Ariel’s Neighborhood

Yesterday and early this morning, while talking about our impending move to a new apartment a few blocks away in a much bigger building (and no longer on the ground floor), Alaina and I talked about how being in a larger complex essentially acts as a fairly effective form of security through obscurity. Unfortunately, as always seems to be the case, the conversation was prescient.

I'm always embarrassed when my education fails me.  Last night while at dinner with friends, I was asked what "H1N1" meant.  I quickly responded with a guess that it was the chemical composition of the core antigenic part of the virus.  One hydrogen, one nitrogen.  Not only was that wrong, but it doesn't even make much sense from a chemical standpoint.  So, I'm here to set the record straight.

What is "H1N1"

Aside from the "butt" of a fantastic joke, it is a serologic classification which identifies the exact subtype of the influenza virus. You see, there are two main proteins on the envelope of the influenza virus—hemagglutinin (H!) and neuraminidase (N!)—that are critical to the mechanism of infection and replication of the influenza virus.  These two proteins are known to exist in a number of different configurations, 16 for hemagglutinin and 9 for neuraminidase[1]  and each configuration is numbered. This means that H1N1 is hemagglutinin type 1 and neuraminidase type 1. H1N1 has the same hemagglutinin protein structure as H1N2 and the same neuraminidase protein structure as H5N1.

Why is this important?

This stuff isn't just taxonomic fluffery.   For those who don't know or remember, the proteins which exist on the surface of a pathogen and the structure of those proteins is like a key which fit very particular locks (receptors) on the surface of the certain of the body's cells creating some change in the cell.  Changes in these configurations can completely alter the way that the pathogen works.  Because these proteins are so unique, they are also markers that the body remembers and recognizes in its immune response and hence are critical to the creation of vaccines against the pathogens.

In short, these proteins are the critical actors in both the mechanisms of infection and the identifiers in the war against them.

Particular to the influenza virus and our two proteins, Wikipedia tells us that Hemagglutinin "mediates binding of the virus to target cells and entry of the viral genome into the target cell" and neuraminidase "is involved in the release of progeny virus from infected cells".  To use a metaphor, if flu virus infection was a bank robbery, hemagglutinin would be the explosives expert responsible for blowing a hole in the wall of the bank and neuraminidase would be the safe cracker and getaway man.

Different configurations of these proteins present differently-abled virus subtypes.  One configuration may be more resistant to conditions outside of the body, another might be more easily communicable from host to host, others might have more devastating effects on the infected host. So knowing what virus we're dealing with not only helps us develop a vaccine, but also informs us of its typical characteristics.

What is swine flu?

You may have noticed recently that the World Health Organization and other related agencies just stopped calling the virus the "swine flu" and started calling it by its scientific name Influenza type A subtype H1N1.  Some falsely believe that this was a worldwide response to cries of foul from pig farmers worried about their business, to stem the worldwide panic causing countries to slaughter pigs and the general public to have sworn off bacon and other lesser pork products.  While those factors all certainly exist, in fact, this was the correct thing to do epidemiologically speaking.

"Swine flu" is just a generic term for any influenza virus that is transmitted between pigs.  Once the flu crosses over to another species, like us, it's no longer a "swine flu" but a "human/dog/seal/bird flu of swine origin".  So calling the current Influenza A H1N1 virus a swine flu doesn't cirrectly communicate the human-to-human transmissibility aspect of the virus.  H1N1 has, just like in 1918, become a "human flu".

Related Articles

• jay.vox.com: Why is swine flu more dangerous than normal flu?
  
• Fluidinfo.com: A few comments on pandemic influenza
• Fluidinfo.com: OK, it’s a pandemic. Now what?
• virology.ws: Influenza Virus Transmission
• virology.ws: Structure of the Influenza Virus
• Wikipedia: Swine Flu
• Wikipedia: Influenza
• Wikipedia: Influenzavirus A
• Wikipedia: Influenza A virus subtype H1N1
• Wikipedia: 2009 Swine Flu Outbreak

Maxwell's "Pretty Wings". I've been waiting 8 years for him to put out a new record, and two years since I first heard a snippet of this track. Worth the wait.

Bradley Mcalister (forceflow2) tweeted:

I've yet to find anything saying why the pig flu is more dangerous than normal flu. No clue why people are spazzing out #swineflu

Short answer: It's not that swine flu ("pig flu") is more dangerous than seasonal flu ("normal flu"), it's that it (and other flus that affect other species) tends to be more dangerous to the entire human population as opposed to just the very young, very old and immuno-compromised.  And now for the longer answer...

How Influenza Kills

Influenza is a nasty little virus that has been around probably longer than we have.  Most strains, by themselves, aren't much of a killer.  What it does with precision however is greatly reduces your body's ability to fight off other concomitant attackers like pneumonia, staph infections, etc.  However, for that to happen, the host (i.e. victim) pretty much needs to have:

1. No pre-built immune response to the flu virus itself
2. A severely depressed or nonexistent immune system

The first case happens most often in very young children who have never been exposed to the virus or most other things.  In this case, your body takes a while to break down the virus, "figure it out" and then mount an effective campaign against it.  That extra time increases exposure to all of the other nasties and can lead to death.  However, if you live, the immunity is stored away for later, much faster use.

The second case usually happens in the elderly or people who are on immuno-suppressant drugs.  Without an effective immune system, the virus very quickly opens the door wide for the knockdown punch by the other pathogens.

In a normal human who has already been exposed to the influenza virus, a subsequent exposure triggers an immediate and massive immune response (learned from the earlier exposure and filed away).  The battle rages on typically until the immune system wins out, defeats the virus and you have to go back to work.

The key to success here is a fast and strong immune response, which kills off the influenza virus before its friends can kill you.

Seasonal Flu

So then the question is, why, if we have this immune response, do we still get sick from the flu every so often? Shouldn't we just be immune?

The answer is: Yes, if in fact it were the same exact virus, which it is not.  Instead every year the virus mutates (as they are wont to do; something about having read Darwin...).  These mutations are very slight: Small enough to get it recognized by your immune system but just enough to confuse it.  Essentially, these changes cause your body's response to be slightly less effective at the start, but then, the body "figures out" the new strain, quickly changes up and wins, leaving you with an immune response to yet another strain.

Bird, Pig, Dog, Porcupine, Jackalope, Unicorn Flu

The thing is of course, we're not the only ones who get the flu.  There are a number of species that are affected by the influenza virus such as birds, pigs, dogs, seals, etc.  However, each species is affected by different strains and that effect is usually—but not always—exclusive: pig flu only affects pigs, bird flu only affects birds, human flu only affects humans.  The reason for that is basic biology: We are all different and viruses, like nature's ninjas, adapt quickly to any new host in order to maximize its virulence (i.e. ability to survive and spread).  In specializing its attack for one species, it usually gives up its ability to transmit to another.

However, in the normal course of evolving, sometimes a strain that only affects, say, pigs, mutates in such a way that makes it communicable to humans.  So some pig farmer has a pig with the flu, next thing you know, the farmer is sneezing on all of his neighbors and next they're all dead.  The reason is that as stated above, that virus was specialized for the pig meaning both much larger genetic changes than the year-over-year seasonal flu and absolutely no immune response.  For all intents and purposes, you, me, grandma and everyone else are like babes in the woods when a pig flu comes a calling.

Pandemic Flu

When influenza jumps species, it has the potential to cause a pandemic (a global version of an epidemic).  This is an event that is a completely natural part of the evolutionary process and occurs around three times in 100 years.  I want to underscore that point: We will almost certainly have a pandemic event in our lifetime and given what we know of history, it will probably be flu.

The worst of these in recent times was the Spanish Flu of 1918 which lasted 18 months, attacked in three waves and killed somewhere north of 50 million people worldwide. While there's absolutely no reason to believe that's a record that will never be reached again, thankfully flu pandemics are usually not as severe as that one.

To understand why, you have to understand a little bit about the three important factors contributing to the success (or failure) of any virus that aspires to a pandemic:

1. It must be a new and sufficiently different strain to eliminate possibility of an immune response
2. It must be communicable between humans
3. It must be virulent (i.e. able to spread)

The first point I've covered well above.  The second point may seem odd, but it's rather important.  If you have a pig flu that can only be transmitted from pig to human, you either have to have 6 billion pigs or you need a lot of frequent flyer miles and a large animal carrier.  The only way for a virus to spread in a pandemic fashion is if we can infect each other.

So once a virus can spread from human to human, it actually has to do so.  The success of a virus to spread quickly and efficiently is called its "virulence".  There are a couple of issues here.  First, viruses that jump species aren't always so efficient at the whole "contagious" thing.  Sometimes the virus has developed ways of getting between hosts in one species that aren't really relevant or as frequently occuring in the new species.  Sometimes the virus is too fragile to live thrive heartily in the new species for very long.  Like us humans, viruses have to adapt to new environments to be successful and while they may be good at it, that sort of skill takes generations of mutations to happen.

Other problems with virulence occur when the symptoms of a virus happen to close to the time of infection.  You see, the lifespan of a virus looks like this:

infection -> shedding -> symptoms -> resolution

That item between infection and the first sign of symptoms is the time during which you have the virus and are contagious but don't know it.  Highly virulent viruses tend to have a fairly long shedding period and/or mild enough symptoms to alow the host to live normally around others.  AIDS is a perfect example of a virus with a long shedding period.  Ebola is the opposite in that not only do you start to show symptoms less than a day after contracting the virus, but the "symptoms" include melting/explode into a bloody meatsack on the floor and the "resolution" is death.  That sort of thing doesn't give lend itself to a high virulence because showing up to work or for a flight tends to be frowned on in such a state.  However, if you've been making out with pigs all weekend and just got a recent case of the sniffles (wipe nose, shake hands, cough cough sneeze), no one's the wiser or alarmed.

So, what's so scary about this flu epidemic?

This is the all-important question.  Many people are feeling a bit turned off of the media hysteria (which, I must say, is usually a great thing to do) but there are some really important things to consider, the first of which is that the World Health Organization and U.S. Center for Disease Control and Prevention are spinning up to high alert.    This is a very clear sign that there is the potential of worldwide danger and they are two of the leading global organizations who are tasked with keeping the microscopic things from destroying us all and they do a damn good job of it. 

At the same time, when a little outbreak in Kenya can lead to a worldwide catastrophe in short order, it's important that they are a little jumpy.  So,  you have to balance their reaction.  It's neither all media hype nor is it end of the world. Yet...

First, let me say that this blog post is the best informed and informative commentary I've seen yet outside of CDC, the /WHO and *some* news media: A few comments on pandemic influenza.  He outlines a number of the things that are most frightening to me.

Beyond that, there are a few more:

• This strain is a variant of the one that caused the Spanish Flu: H1N1
• Remember up there where I said that most strains aren't killers?  Yeah, well, this one is and a strong immune response (the kind, for example, that people in their 20s and 30s have) is actually the cause leading to cytokine storms.  Here's a vivid description of said phenomenon from the description of the 1918 Spanish Flu outbreak: "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred." The majority of deaths were from bacterial pneumonia, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages and edema in the lung." Oh, the bleeding!  Why must it always be the bleeding?!
  
• The locations of the confirmed cases mean that the infection has already hit the airlines/airports and local quarantine may be fruitless since it would have to be done on a global scale
• The initial outbreak was in Mexico City, at 8.8M people, the largest and most overcrowded city in Mexico.  That's doesn't help with quarantine.
  
• There are confirmed cases in San Diego and near Austin.  Where Jen's family and my parents live.
  

Anyhow, I hope that I've answered some questions that I see on Twitter.  Sorry I couldn't keep it under 140 characters.

Related Articles

• jay.vox.com: What does "swine flu" and "H1N1" actually mean?

Oddly, I was on air on the Jimmy Fallon show for about 10 seconds last night.

I love this guy. The ending might be the best part.