22/10: Vicious little things
There’s a letter to the October 5 Nature1 getting some coverage. Being a bit swamped, I didn’t even notice it until the CBC’s The Current started talking about it the other morning. You’ve probably heard the outlines; it’s got some serious profile. Seems some University of Washington and CDC people put together a ‘reconstructed’ H1N1 virus (along with some related viruses engineered to contain only subsets of the H1N1 set of genes) infected some mice with it, and watched what happened.
Yes, H1N1. That would be Spanish flu. The pandemic strain that wiped out between 50 and 100 million people, back in 1918, and something of a theme, in the blog that preceded this one. Yes, it has, in a sense, been resurrected.
Now I could take a minute and say the first thing everyone is saying:
Yikes. They can do that?
Okay, now that’s out of the way, I should also say:
Cool. They can do that?
It is cool. Extract the viral RNA (these viruses use RNA for their permanent genetic store, such as it is, as opposed to DNA) from a corpse that’s been on ice 90 years, sequence it, build a whole replica virus genome from the fragments. Inject the result into suitably prepared and amenable cells, budda boom, budda bing, the virus genome does what virus genomes do: gets the cells to make a whole pile of fully intact, neatly packaged virus particles, protein coat ‘n all.
Bloody freakin’ brilliant. And one hell of a technical achievement. Not something (fortunately, I’d say) just anyone can do. So, ‘long as the thing doesn’t get out of containment and wipe out a tenth of the world population, bring every economy in the world to a screaming halt and generally reduce our civilization to a shattered, smoking remnant of what it once was, yes, I’m impressed.
Okay, that last bit—the notion of H1N1 being a potential civilization killer—that’s hyperbole, actually. No one seems to think that’s especially likely. H1N1 was a bad bug, but there’s immunity to the family all through the human population, now, even though there probably aren’t a lot of folk still kicking who were actually exposed to that bug in particular. So, presumably, even if it did get out, the percentages would be somewhat less horrific than they were in the tail end of the first world war. It might be pretty ugly—especially given widespread air travel, which wasn’t a factor in 1918—but it probably wouldn’t be quite the apocalypse.
Anyway. Getting away from the scary what ifs to the actual results. The results of the mouse study were: (1) Well, yes, the mice died. (2) The mice infected with the ‘whole’ reconstructed virus got it worst—died fastest, had the most severe symptoms. (3) It looks like most of the damage was done by a severe general immune response—during the course of the illness (and even after the deaths of the mice) the team found extremely high levels of the mRNAs associated with the general inflammatory immune response the body uses to destroy tissues infected with potentially dangerous (but as yet unknown to the body) pathogens.
That last result, incidentally, is a confirmation of something that had been long suspected about H1N1 (and which is generally suspected about H5N1—or Avian flu—as well). That being that most of the damage done to the body isn’t done directly by the virus but by the body’s own immune system, which seems to overreact in extreme fashion when H1N1 shows up.
Oh, and (4) they’ve got a vaccine. Which is good, actually. Yes, it’s a vaccine for a pathogen that doesn’t (we think) exist outside the CDC’s containment facility, and it was tested on mice, but knowing how to do this, theoretically, gets us a step forward toward dealing with H5N1, should it go all pandemic on us one day too.
But getting to that ‘vicious’ thing: the team finished the study fairly sure they’d identified one receptor in particular that the virus proteins stimulated, and which might be the cause of the runaway immune response. And, interestingly, though certain of the virus proteins seemed more significant than others in terms of causing said stimulation, it was, remember, the whole viruses (with the whole genome) which were the deadliest.
So one guy, at least—a commentator on the radio program I heard—was speculating that, in fact, there might be a very good reason (good for the virus) it does what it does. That, in fact, that particular capability—causing the host’s immune system to panic and cause vast amounts of damage—might be to the virus’s advantage, natural selection wise.
He didn’t, however, go on about how having the host blow its lung tissues to pieces with its general immune response might be to the virus’ advantage. And I’ve been unable to find anyone else commenting on this, so I’m left to wonder if the notion was something to do with either (a) the general immune response creating conditions in which the virus could more easily spread through the tissues, or (b) the general immune response wreaking such havoc that the body couldn’t even marshall a more useful specific immune response.
Either way, it’s sort of a creepy thought. And while it’s not particularly logical to ascribe intentions or emotion to a virus—a bit of protein with a handful of DNA or RNA genes inside clearly has neither—I can’t help thinking this, picturing the bizarre image of how this one works. Considering the unsettling picture of the general immune system pounding the hell out of its own body in a misguided attempt2 to stamp out the infection, I can’t help saying to myself:
Damn. That’s one vicious little bug.
1 Kash, John C. et al, “Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus”, Nature, Vol 443, 5 October 2006, pp. 578-581
2 I only just managed to restrain myself making the comment in the general body, but sure, as this is ‘let’s find ways to mix biology and politics’ week, I do find an odd parallel here with one of the issues du jour. Yes, the virus gets the host to destroy itself through a hugely overwrought defensive reaction… Which has some parallels with using violence to panic a population into accepting the enactment of regressive measures—thereby turning a relatively open society into a much more paranoid and unpleasant one, and drawing their military into bloody, expensive quagmires, costly to the economy and to political stability.
Yes, H1N1. That would be Spanish flu. The pandemic strain that wiped out between 50 and 100 million people, back in 1918, and something of a theme, in the blog that preceded this one. Yes, it has, in a sense, been resurrected.
Now I could take a minute and say the first thing everyone is saying:
Yikes. They can do that?
Okay, now that’s out of the way, I should also say:
Cool. They can do that?
It is cool. Extract the viral RNA (these viruses use RNA for their permanent genetic store, such as it is, as opposed to DNA) from a corpse that’s been on ice 90 years, sequence it, build a whole replica virus genome from the fragments. Inject the result into suitably prepared and amenable cells, budda boom, budda bing, the virus genome does what virus genomes do: gets the cells to make a whole pile of fully intact, neatly packaged virus particles, protein coat ‘n all.
Bloody freakin’ brilliant. And one hell of a technical achievement. Not something (fortunately, I’d say) just anyone can do. So, ‘long as the thing doesn’t get out of containment and wipe out a tenth of the world population, bring every economy in the world to a screaming halt and generally reduce our civilization to a shattered, smoking remnant of what it once was, yes, I’m impressed.
Okay, that last bit—the notion of H1N1 being a potential civilization killer—that’s hyperbole, actually. No one seems to think that’s especially likely. H1N1 was a bad bug, but there’s immunity to the family all through the human population, now, even though there probably aren’t a lot of folk still kicking who were actually exposed to that bug in particular. So, presumably, even if it did get out, the percentages would be somewhat less horrific than they were in the tail end of the first world war. It might be pretty ugly—especially given widespread air travel, which wasn’t a factor in 1918—but it probably wouldn’t be quite the apocalypse.
Anyway. Getting away from the scary what ifs to the actual results. The results of the mouse study were: (1) Well, yes, the mice died. (2) The mice infected with the ‘whole’ reconstructed virus got it worst—died fastest, had the most severe symptoms. (3) It looks like most of the damage was done by a severe general immune response—during the course of the illness (and even after the deaths of the mice) the team found extremely high levels of the mRNAs associated with the general inflammatory immune response the body uses to destroy tissues infected with potentially dangerous (but as yet unknown to the body) pathogens.
That last result, incidentally, is a confirmation of something that had been long suspected about H1N1 (and which is generally suspected about H5N1—or Avian flu—as well). That being that most of the damage done to the body isn’t done directly by the virus but by the body’s own immune system, which seems to overreact in extreme fashion when H1N1 shows up.
Oh, and (4) they’ve got a vaccine. Which is good, actually. Yes, it’s a vaccine for a pathogen that doesn’t (we think) exist outside the CDC’s containment facility, and it was tested on mice, but knowing how to do this, theoretically, gets us a step forward toward dealing with H5N1, should it go all pandemic on us one day too.
But getting to that ‘vicious’ thing: the team finished the study fairly sure they’d identified one receptor in particular that the virus proteins stimulated, and which might be the cause of the runaway immune response. And, interestingly, though certain of the virus proteins seemed more significant than others in terms of causing said stimulation, it was, remember, the whole viruses (with the whole genome) which were the deadliest.
So one guy, at least—a commentator on the radio program I heard—was speculating that, in fact, there might be a very good reason (good for the virus) it does what it does. That, in fact, that particular capability—causing the host’s immune system to panic and cause vast amounts of damage—might be to the virus’s advantage, natural selection wise.
He didn’t, however, go on about how having the host blow its lung tissues to pieces with its general immune response might be to the virus’ advantage. And I’ve been unable to find anyone else commenting on this, so I’m left to wonder if the notion was something to do with either (a) the general immune response creating conditions in which the virus could more easily spread through the tissues, or (b) the general immune response wreaking such havoc that the body couldn’t even marshall a more useful specific immune response.
Either way, it’s sort of a creepy thought. And while it’s not particularly logical to ascribe intentions or emotion to a virus—a bit of protein with a handful of DNA or RNA genes inside clearly has neither—I can’t help thinking this, picturing the bizarre image of how this one works. Considering the unsettling picture of the general immune system pounding the hell out of its own body in a misguided attempt2 to stamp out the infection, I can’t help saying to myself:
Damn. That’s one vicious little bug.
1 Kash, John C. et al, “Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus”, Nature, Vol 443, 5 October 2006, pp. 578-581
2 I only just managed to restrain myself making the comment in the general body, but sure, as this is ‘let’s find ways to mix biology and politics’ week, I do find an odd parallel here with one of the issues du jour. Yes, the virus gets the host to destroy itself through a hugely overwrought defensive reaction… Which has some parallels with using violence to panic a population into accepting the enactment of regressive measures—thereby turning a relatively open society into a much more paranoid and unpleasant one, and drawing their military into bloody, expensive quagmires, costly to the economy and to political stability.
