A Century After 1918 Flu, A Virus that Still Surprises

This month marks the centennial of the first case of one of the world's deadliest flu outbreaks, which was reported on a Kansas army base. It is estimated that the 1918 flu infected 500 million people around the world and killed 50-100 million. With the 100^th anniversary, we sat down with graduate student Spencer Fox, who studies the flu virus and flu pandemics.

As you have studied flu, what are some of the things you learned that surprised you?

I think the thing that constantly surprises me about the flu is that it's constantly surprising us. We have learned a lot about the flu since 1918. We've developed flu vaccines and antiviral drugs. We've learned a lot about how our bodies' immune systems react to flu infections. We've learned so much, and yet, when you combine everything we've learned, we still get things wrong. Originally, we thought the vaccine wasn't that effective this year, but it turns out more recent reports say it actually was. All of the original reasons we thought this seasonal flu epidemic was going to be a bad one didn't turn out to be true, but it was a really bad flu season. There's going to be a lot of research to find out why that was and I think we're going to learn some really new things about the virus. We're constantly learning about it.

What do we know about that 1918 outbreak now that people didn't know at the time?

The flu virus hadn't even been molecularly identified at that time. The illness hadn't been identified as a virus yet. We didn't have vaccines. We didn't have mass antibiotic distribution at that time.

How did the 1918 flu influence scientific understanding and propel us towards better understanding of the flu and other diseases?

I'm not a historian, but my feeling is that the pandemic showed how devastating these epidemics and pandemics could be even with our understanding from the scientific advances made in the 19^th and early 20^th century. Because of that quite a bit of funding was given to studying infectious diseases, not just the flu, and I think today we're still funding quite a bit of research because of the 1918 flu.

Spencer Fox

Do you think we'll ever see an outbreak like the one in 1918 again? Have we advanced beyond its ability to kill us on that level?

Flu is always surprising us, so it's possible, but I think things have changed so much that it would be very, very surprising if there was a flu pandemic that was just as bad as 1918. Just the invention of vaccines puts us ahead. In 2009 when that H1N1 pandemic emerged, the CDC had a vaccine ready in something like six or seven months. The thing a lot of people don't realize about vaccines is that even if they don't prevent you from getting the flu they have very strong protection against dying from the flu. So, we would certainly see reduced mortality because of our ability to produce vaccines. Plus, we have antivirals and we also have antibiotics, which are really important because often times people with flu infections will die from bacterial pneumonia infections, so antibiotics can help with that. … That's not to say that it wouldn't be devastating to health care systems. We've seen even with this most recent seasonal flu epidemic that our health care systems are susceptible to being overwhelmed by flu epidemics. This year, they're expecting to see more than 50,000 people killed by the seasonal flu in the U.S. alone.

What are some of the most interesting things you've learned about the 1918 outbreak?

The age distribution of the mortality. Normally, when you have flu epidemics you think of the most susceptible populations being the very young newborns and the very elderly, and those people tend to experience the highest rates of mortality. During the 1918 pandemic, we saw this weird trend where it was people in their 30s, the normally healthy individuals, who had the highest rates of mortality. That's a strange phenomenon that has sparked a lot of research.

Has anyone come up with good theories about why that distribution existed?

In just the last few years, we've kind of figured out why, and it all comes back to the way our bodies respond to flu viruses immunologically. There's an idea that's been around for a while but has recently gained a lot of support. It's called original antigenic sin. To understand flu immunity you need to understand the currently circulating flu. You've probably heard that there are multiple strains of flu circulating at any one time. There is the type classification, Flu A and Flu B. Then, you get into the subtype, like H1N1 or H3N2. These Hs and Ns and the numbers correspond the antigens on the virus particle. Those are the proteins that our bodies respond to. The 1918 flu was an H1N1.

So, traditionally what we thought was that our bodies' reactions to H1N1 versus, say, H3N2 were kind of independent of one another. It didn't matter whether you were infected with one or the other, they didn't provide immunity against each other.

With, original antigenic sin, basically whatever your first flu virus infection, whatever the subtype of that infection is, that dictates your lifelong susceptibility to other flu viruses. You'll have higher protection against that subtype and lower protection against other subtypes. It's not clear if that protection means you're less likely to get infected, but it seems you're less likely to die. You'll have a stronger ability to fight off a virus of the subtype that is closely related to the subtype you were first infected with.

Does this theory explain why the 1918 pandemic was deadlier to a certain group?

The idea is that you can look at the prevalent flu subtypes through time. You can figure out that an 18-year-old in 1918 was born in 1900 so you can look to see what prevalent subtypes were around then try to understand their susceptibility to an H1N1. The basic idea is that individuals in the age group that suffered the highest levels of mortality were the ones that were primed with a subtype that was not related to H1N1. There was an H3N8 pandemic in 1889. So that pandemic primed people with the incorrect subtype to fight off the outbreak in 1918. From 1889 to 1918 is almost 30 years and so you saw the highest levels of mortality in that age group.

What steps are scientists taking to make sure there isn't a similar outbreak?

There are large flu surveillance systems currently in place that are constantly looking for new subtypes or novel combinations of the H and N. They are across the globe. The idea is that if we can identify a novel flu strain early on then we can shorten the time for being able to produce a vaccine. Those surveillance systems are set up to look at human populations, but they are also now looking at livestock populations because oftentimes these novel subtypes emerge in livestock and transmit to humans. …

Whenever you get these new subtypes it means the population may not have immunity to that subtype. Our research has looked at pandemic emergence timing and what we found was that pandemics emerging in the northern hemisphere have all emerged in the spring and summer months. That was intriguing to us because you normally think of the flu as being a winter disease. And so, we developed the hypothesis that there is this generalized immunity that infection with a flu virus will protect you for about a month from any other type of flu virus.

Are there any lessons that non-scientists can take from the 1918 outbreak?

We know a lot more about how these things are transmitted. If there was a pandemic as bad as 1918 there would be preemptive school closures and people would probably stay home from work. If we were able to isolate everyone for a few weeks, the epidemic would die down. So, we know a lot of things along the intervention side of things.

Other than washing your hands, not going to work if you're feeling sick and getting vaccinated, I think the main thing that I would advocate for is this idea of global health. The pandemic in 1918, as well as more recent events like Ebola or Zika, have showcased how we can't treat the public health of the U.S. as a silo independent of the rest of the world because diseases don't see the borders of our country. So, there have been a lot of articles recently about how the CDC may be cutting funding to global health infrastructure by potentially as much as 80 percent and I think those types of ideas are very short sighted.

What disease are you most afraid of catching?

Rabies. The rabies virus is almost one hundred percent deadly in people that don't receive immediate treatment. Basically, by the time you start seeing symptoms in your body, it's already too late to treat it. Rabies is a very uncommon disease, thankfully.