• Alex Cloherty

A different kind of mix & match

Updated: Jun 15

Today's post stemmed from a conversation in a group chat. My friend James asked, "Do we have a good theory on why influenza became less deadly after the influenza pandemic of 1918-1920? Wikipedia seems to claim that people were just malnourished, dirty, and overcrowded after World War 1. I guess to specify, my question is, do we think that influenza mutated to become less deadly?"

A very good question indeed James.

In my first, brief, incomplete answer, I wrote back, "Basically, influenza is more deadly every time there is a major jump in host species."

But why is that the case? And how does influenza accomplish these jumps? It's quite remarkable - influenza jumping from being able to live in birds, to being able to live in humans. It would be kind of like a human suddenly developing the capacity to flourish sans-space-station on Mars. So, how does it work?

Well, to understand the answer, you first have to have an idea of how influenza is built. Usually, when one thinks of genetic material, one imagines one strand of DNA, like this -->

Photo credit goes to my friend Sven Beveridge, a professional furniture designer and 		maker who accepted a challenge to re-create DNA in the workshop. Hit him up if you want some beautiful woodworking done in South Holland.

Photo credit goes to my friend Sven Beveridge, a professional furniture designer and maker who accepted a challenge to re-create DNA in the workshop. Hit him up if you want some beautiful woodworking done in South Holland.

However, that's an incomplete picture in some cases. For instance, the code for a human is written out over 46 strands of DNA like this. House cats have 38. Dogs have 78. The Adder's tongue fern has 1440. Take from that what you will.

Like different plants and animals, different viruses can also have different amounts of genetic material. For example, Influenza A, one of the main types of flu that infects humans, has 8 strands of genetic material. For the nerdier of the readers, in the case of Influenza that genetic material is not actually DNA, but rather RNA - but that's not the main point in this story. The main point is that, kind of like how every individual human cell has 46 strands of genetic material, every individual Influenza A virus has 8 strands of genetic material. So, something like this:

This feature of the flu virus underlies its ability to evolve in two distinct ways, which in turn explains why sometimes influenza causes pandemics, and then thereafter it typically peters out into a mere seasonal flu.

The first way in which flu can evolve is more like us: slowly, incrementally, over long(ish) periods of time. This is the kind of evolution that happens due to small random mutations (changes) in the genetic code of the virus - just like the kind of evolution that allowed humans to evolve from our hominid ancestors. This type of evolution can be thought of as the work of an imperfect photocopier, acting on the printed page of the genome. Over time, the photocopier of evolution starts turning some "i"s into "l"s and some "B"s into "H"s and the story on that paper gradually changes. That "story" being the living thing that is encoded within the writing on that paper genome.

In terms of our human relationship with influenza, this slower evolution is the safer type of influenza evolution. Typically it generates a new, but not too-new, seasonal flu each year, which isn't exactly the same as last year's flu, but pretty close. Our body can therefore vaguely recognize the new seasonal flu as most likely being bad news, because it looks and acts kinda like last year's seasonal flu.

Then, we get to the worse (from the human perspective) type of influenza evolution, which can occur due to influenza having not one, but eight of those strands of genetic information. Each of those eight strands contains the code for creating a different part of the virus - and each of those eight strands have different versions. You can think of it like Lego. The first strand might code for a 2-pronged blue block, the second strand for a 4-pronged orange block, the third strand for an 8-pronged red block, and so on until you've built one virion of influenza. But, different types of strands can swap out: you build a different virus if you instead combine a 2-pronged purple block, a 4-pronged white block, and an 8-pronged yellow block. And, you get yet another virus if the blue/orange/red and purple/white/yellow viruses are both infecting the same animal at the same time - their genetic codes mix and match and create a brand-spanking new virus that looks very different that anything any human immune systems have seen. Blue/white/red. And that is where we run into problems.

You see, sometimes these mix-and-match events will give a flu that formerly only infected birds, or pigs, or another non-human animal, the precise genetic Lego block it needs to provide the virus with a brand-new ability to infect humans. Thus, the bird-to-human jump is made. And if this new virus indeed infects humans, our immune systems will be totally unprepared, leaving us rather vulnerable to get very sick. And voila, there you have it: an influenza pandemic.

In the case of this latter, more rapid, "genetic shift"-type (as virologists call it) evolution, a particularly deadly flu like the one responsible for the 1918 pandemic can emerge, and quickly rip through a population. And then, after it gets in to the human population, usually it is there to stay. After a "genetic shift", that new flu, i.e. the blue/white/red one, will usually kind of take over for the coming years as a seasonal flu. Each year, it will undergo some small mutations and evolve in the former, slower way ("genetic drift"). As a result, it will be a bit different than it was the previous year - which explains why we need updated flu vaccines every flu season. But, usually it won't have mutated so much that it becomes unrecognizable to our immune systems. That means that people who had the previous year's flu typically have still some immunity to the following year's flu - because the virus is still similar enough for their immune system to recognize.

This concept may also explain why in 1954, when there was a breakout of the same kind of flu as 1918, it hit younger people much harder than older people - because the young people merely had developed immunity to the more recent seasonal variations, which were very distant cousins of the 1918 version. In contrast, the older people had actually "seen" the 1918 version and thereby their bodies knew exactly what to do with the highly similar 1954 flu.

And, how does this compare to the novel coronavirus, of COVID-19? Well, you'll have to check out the next Microbial Mondays post to find out.

Until next time - let's celebrate the good news about the other kind of mix-and-match!

~ Alex

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