How Plagues Really Work
February 19, 2015 8:10 AM   Subscribe

So what is wrong with listening to the drumbeat, to the endless calls to protect ourselves against the coming plague – against Ebola from Africa and bird flu from Asia? Is it possible that a huge pandemic could erupt from some as-yet unknown pathogen? Is apocalypse lurking out there, among rats or monkeys, or bats or flying squirrels or birds? The Black Death shows that you can never say never: there might be an animal pathogen out there that, under the right circumstances, can evolve and maintain both virulence and transmissibility among humans as well as animals.
posted by ellieBOA (22 comments total) 8 users marked this as a favorite
The next pandemic will probably come from a farm in China, like most of the previous ones in the last couple of decades.

There's a strain of flu that can infect humans, and a different one that can infect geese and ducks. Humans can't get the bird flu, and birds can't get human flu.

But pigs can get them both, and if they are simultaneously infected with both of them, it's possible for the genes to mix, resulting in new strains of flu which can turn out to be particularly deadly.

It's an open secret in medical circles that China's collectivized farms are where nearly all of that happens, because they keep ducks/geese and pigs together. It isn't talked about much, however, because it would embarass the government of the PRC and the researchers would lose their access to China, and have less warning when new strains appear.
posted by Chocolate Pickle at 8:18 AM on February 19, 2015 [5 favorites]

Day 1

[Spoiler for Steven Soderbergh's 2011 film Contagion]
posted by Fizz at 8:22 AM on February 19, 2015 [1 favorite]

Chocolate Pickle, the whole point of the article was that the next big pandemic might well be a mutation of an existing human disease, not a new animal-human crossover. You've restated the claim the article is arguing against, without addressing the points the article raises about the relative chances of the evolution of cross-species transmissibility and the evolution of high virulence.
posted by Fraxas at 8:39 AM on February 19, 2015 [5 favorites]

From the article:
There is nothing new in the intimate contact between animals and people. Our hominid ancestors lived on wildlife before we ever evolved into Homo sapiens: that’s why anthropologists call them hunter-gatherers, a term that still applies to some modern peoples, including bushmeat hunters in West Africa. After domesticating animals, we lived close beside them, keeping cows, pigs and chickens in farmyards and even within households for thousands of years. Pandemics arise out of more than mere contact between human beings and animals: from an evolutionary point of view, there is a missing step between animal pathogen and human pandemic that’s been almost completely overlooked in these terrifying but entirely speculative ideas.

According to the evolutionary epidemiologist Paul W Ewald of the University of Louisville, the most dangerous infectious diseases are almost always not animal diseases freshly broken into the human species, but diseases adapted to humanity over time: smallpox, malaria, tuberculosis, leprosy, typhus, yellow fever, polio. In order to adapt to the human species, a germ needs to cycle among people – from person to person to person. In each iteration, the strains best adapted to transmission will be the ones that spread. So natural selection will push circulating strains towards more and more effective transmission, and therefore towards increasing adaptation to human hosts. This process necessarily takes place among people.
posted by TheophileEscargot at 8:41 AM on February 19, 2015 [8 favorites]

Fascinating share. I find this extremely relevant when talking about modern day communicable diseases, especially in light of the recent Ebola scare.
posted by Capillus at 8:56 AM on February 19, 2015

I notice that news aggregators and many sites are reporting a "superbug outbreak at UCLA" this morning.

Makes this a rather timely post....
posted by CrowGoat at 9:09 AM on February 19, 2015

One thing that IS different about modern Chinese (and American) factory farms as opposed to historical farms is the sheer density of animals kept in the same location. We know that high density encourages the evolution of high virulence by lowering the biggest cost of high virulence--that is, the possibility of killing your host before you get a chance to infect a new one. High density also often stresses animals out, which lowers their immune response to various diseases--which is part of why American farmers routinely supplement animal feed with antibiotics. I'd argue that is why these farms--in particular farms where birds and swine are kept intermixed--are a particularly nasty breeding ground for respiratory illnesses like flu. I'd rather something jump from animals to people that isn't already adapted for spreading quickly and destructively through very dense host species, please.

(And that goes for American factory farms too. As far as I can tell, the only difference there is the species present--Americans usually go in for monoculture these days.)

Honestly, I'm kind of dubious about the article's point. Yes, it's definitely possible for diseases to evolve increased virulence and therefore increase transmissibility after they're established in a new species--you honestly pretty much expect that if the new host species is dense enough that finding and infecting new hosts is relatively easy for the pathogen. That hasn't been new in infectious disease work for a long time.

As far as I can tell, the take-away from the article is that we should treat diseases that have newly jumped from animals to humans as a worrying potential threat rather than an immediate one, because they won't necessarily have gotten good enough at jumping from humans to humans yet and we can more easily quash them before they get a chance to evolve that ability. Which, yes.... how is that different from the way that epidemiologists handle transmissions like that now, again?
posted by sciatrix at 9:15 AM on February 19, 2015 [2 favorites]

I notice that news aggregators and many sites are reporting a "superbug outbreak at UCLA" this morning.

Personally I'm much more worried about "superbug" CREs and multi-resistant infections than a single new strain racing across the world like 1918. Overuse of anti-biotics is creating stronger, more resistant versions of everyday bacteria, and not enough is being done to develop new solutions. When these extremely resistant strains become established in the wild, it'll take us back to the 16th century, before the germ theory, when we have no effective tools for fighting simple, everyday infections and simply cutting yourself on a park bench is a life threatening event.
posted by T.D. Strange at 9:26 AM on February 19, 2015 [4 favorites]

When I read "take us back to the 16th century," it's time for me to stop reading a thread. I need my sleep.
posted by Camofrog at 9:39 AM on February 19, 2015

I prefer my park benches less "cutty".
posted by DaddyNewt at 10:05 AM on February 19, 2015

Not sure about viruses, but they have discovered a new antibiotic which appears to be immune to bacteria developing resistance. They found it in dirt. Still researching it, according to the podcast here, it will take about 2 years before they get to clinical trials.
posted by Marie Mon Dieu at 10:29 AM on February 19, 2015 [1 favorite]

The next pandemic will probably come from a farm in China, like most of the previous ones in the last couple of decades.

On the specific subject of influenza, China certainly has the sheer-number advantage, but living in close quarters with pigs and a handful of chickens is sort of a worldwide subsistence farming tradition. The flu in 2009 probably came from Mexico, and hypotheses about the origin of the 1918 flu include France, China, and Kansas.
posted by Blue Jello Elf at 10:32 AM on February 19, 2015 [2 favorites]

discovered a new antibiotic

Previously, with the best overview article here.
posted by ambrosen at 10:54 AM on February 19, 2015 [1 favorite]

I felt like this article was trying to make a really good point, but it didn't come out quite strongly enough in the conclusion. Scary diseases like ebola and bird flu get tons of media attention and lots of money thrown at them while they're grabbing headlines, but what we really need to help prevent pandemics are decent living conditions and basic sanitation for everyone on the planet. Unfortunately it's a lot less sexy to provide housing for refugees or clean water in places that lack it, compared to curing some terrifying new disease. That was my take-away from the article: diseases are going to jump from animals into humans, but our attention needs to be on taking care of our human living conditions so that those newly-arrived diseases don't have a chance to develop into pandemic strains.
posted by vytae at 11:41 AM on February 19, 2015

This is basically a brief and insufficient gloss on Ewald's work, which Ewald presented thoroughly twenty-one years ago in his 1993 book Evolution of Infectious Disease -- a fascinating and important book I've been recommending for many years.

I say that Orent's article is "insufficient" because she doesn't explain at all the key element in this model of virulence: vector.

First, though, a quick overview (and recapitulating the beginning of the piece): traditionally, the scientific consensus about virulence, based upon both evidence and a first-pass Darwinist analysis, is that basically parasites evolve toward symbiosis and pathogens toward decreasing virulence because the host's overall fitness is closely coupled with, obviously, the quality of the pathogen's environment. You kill your host, you're burning down your home. Or blowing it up. That's not a very successful strategy, generally.

And, really, all things being equal, this model of the evolution of virulence makes a lot of sense and there's just enormous amounts of evidence that this is usually the case.

For example, one of the most successful and well-known class of human pathogens are the rhinoviruses that cause the common cold. We don't know that they evolved from more virulent viruses, but it's striking how little virulence they have. And it works extremely well for them! We get infected and we almost always just continue to go about doing what we do -- walk around, rub our noses, sneeze, shake people's hands and open doors and so on -- we're a walking combined nursery and mass transit system for rhinoviruses. As Orent writes, our bodies have numerous mechanisms with which it either rids itself of infectious/foreign bodies, or the byproducts associated with that fight, and so pathogens will often opportunistically trigger those things as part of its strategy (forgive me for speaking teleologically -- of course there's not an actual goal or strategy, but it's convenient to talk this way).

The point is that very often the selective pressure is going to be don't kill the host. In fact, don't really make the host any more sick than is necessary. The biggest bottleneck is the vector between hosts -- true, a pathogen can be fantastically successful in a limited sense by maximizing its reproduction within a host such that it utilizes as much of the available resources as quickly as possible and making the greatest number of copies of itself. But if that kills the host in six hours and the host drops dead and lay there on the ground for two days in increasingly hostile conditions and with direct contact with similar hosts less and less likely, that's not a successful strategy at all.

The takeaway here should be, basically, the host itself is the transmission vector. The pathogen needs the host to bring the pathogen into contact with other hosts. This generally means that the host should be ambulatory.

Now, take this way of thinking about that selective pressure for/against virulence and ask yourself: what happens if the host isn't the vector? What happens if there's a third agent that is the transmission vector between hosts? In that case, the maximize-reproduction-and-quick-host-death might turn out to be the most successful strategy. This is still going to be sensitive to other selective pressures, but this is the basic idea.

If you look at the most common infectious diseases, there's a strong pattern. The least virulent are transmitted person-to-person by ambulatory hosts, as with the common cold. The most virulent of the common human infectious diseases are transmitted by a third agent -- such as an external vectors like mosquitoes (malaria) or contaminated water from diarrhea (cholera and others).

This is the missing connection between what Orent explains in her article and her conclusion about "disease factories".

Ewald's (unproven and, as it happens, probably wrong -- but I'll get to that in a moment) theory is that the 1918 flu pandemic was the result of a less virulent strain of influenza quickly evolving to be much more virulent in the very peculiar environment of WWI army trenches and hospitals, which was that soldiers were in very close proximity to each other for extended periods and, when incapacitated by illness, were cycled between the trenches, hospitals, and field hospitals. Technically in this example the soldiers were still the transmission vector, but they were being continually cycled between sick and healthy populations, often not even under their own power.

I should digress for a moment and explain that pathogen evolution measurably proceeds, and sometimes quite rapidly, within individual hosts during a given infection. Not only are pathogens competing with other pathogens, as a pathogen reproduces during an infection it will mutate and strains of itself will compete with each other. So even within a single infection a pathogen can evolve toward significantly greater or lesser virulence.

Now, as it happens, in Ewald's 1993 book he went out on a limb and hypothesized that both the 1918 flu and HIV are examples of this evolution of an endemic low-incidence, low-virulence pathogen toward high-incidence and high virulence. Unfortunately for him, he was wrong on both counts. I believe that we've since managed to somehow get a partial sequence of the 1918 flu (I'd appreciate a correction on this if I'm mistaken) that shows that it was closely related to an influenza in another species and it jumped. And we pretty much know with certainty that this is the case with HIV -- it jumped from monkeys to humans sometime in the middle of the twentieth century in central Africa (IIRC). So the whole species-jumping model is validated by these two very high profile examples, as well as many other epidemics that haven't been global.

This doesn't mean that Ewald's model of the evolution of virulence is wrong, however. It just means that you shouldn't think in terms of it necessarily being one or the other. Orent makes some good arguments for why we shouldn't overestimate how crucial species-jumping is to high-virulence epidemics. But we know with a certainty that this happens, that it's a reliable way that new, virulent diseases appear in populations.

But we have a number of smaller-scale examples which very strongly fit Ewald's model, and frankly they're terrifying. Orent doesn't mention what I think is the most horrifying and vivid examples, which Ewald spends quite a bit of time on: neonatal units in hospitals. There have been a number of extremely virulent and extraordinarily difficult to eradicate outbreaks in neonatal units. In those cases, the transmission vectors are primarily the nursing staff. This is a general problem in hospitals -- all these pathogens which otherwise rely upon relatively healthy hosts for transmission are instead in environments where health care workers and other aspects of the environment are available as the primary transmission vectors between hosts. When you couple this with the selection pressures of how antibiotics are used, then you get environments that are optimal for evolving maximal virulence.

Ewald and others have been building two related fields -- evolutionary epidemiology, and evolutionary medicine. Both have very important public health policy implications. One of the arguments that Ewald makes in his book is that palliative care which keeps people functional while not directly fighting the infection, and social customs and policies which encourage people to be ambulatory and functioning socially when they're ill, mean that we're choosing to create an environment where pathogens are freer to move in the direction of increasing virulence. If we can mask most of the flu symptoms and we insist that workers and children show up when they have the flu, then the flu virus is encouraged to be as virulent as it can get away with being. To which you might respond: so? But think about what that means for the folk who are less healthy, and those who are more vulnerable like the very young and the very old.

One of Ewald's chief arguments is that viruses and bacteria evolve much more quickly than we will ever be able to match with pharmaceuticals. We need to start thinking about how we approach medicine and health policy such that we're using evolution to our advantage and not to our detriment.

I think it's unfortunate that Ewald staked so much on his hypotheses about the 1918 influenza and HIV, because I think it hurt his credibility some. But there's a whole body of research the demonstrates that while it's probably not the case that most such pandemics follow this model (I think the last twenty years and sequencing have given us a lot of evidence for species-jumping being really important), it's likely that some do and we're making a big mistake if we ignore this. More to the point, the relative likelihood is dependent upon what's actually happening in the world, in both models. We can be creating more and more intense opportunities for these species-jumping pandemics to emerge, or we can be creating more and more intense opportunities for quick evolution torward virulence pandemics to emerge. Or worst ... we could be doing both. We probably are doing both. But Orent's point is very valid in that we're pretty much not expecting the latter.
posted by Ivan Fyodorovich at 12:58 PM on February 19, 2015 [18 favorites]

Is apocalypse lurking out there, among rats or monkeys, or bats or flying squirrels or birds?

So there really are poison monkeys s'what you're saying?
posted by sour cream at 1:27 PM on February 19, 2015

Ivan, your comment made me think of that outbreak at the NIH hospital a couple years ago.
posted by Blue Jello Elf at 1:28 PM on February 19, 2015

"... it jumped from monkeys to humans..."

That should be "chimps", by the way, not monkeys -- I know that it's related to SIV and I know that monkeys aren't chimps, but for some reason when I was writing I was thinking specifically monkeys.

posted by Ivan Fyodorovich at 1:40 PM on February 19, 2015

I love apocalyptic scenarios more than most people, probably because, like most people, I'm reassured knowing these things are extraordinary and unlikely and oh so exotic, and they always happen to other people in other places.

The world got a little smaller for my family in the last 2 weeks, when a relative tore his hamstring cross country skiing (in New England) and ended up with an infection. Within 24 hours he was diagnosed with necrotizing fasciitis and shipped off to the regional facility in a medically induced coma. They got his heart starting again when that stopped. They got his liver working again when that stopped. Astonishingly, he has his leg (what's left of it).

I'm not really sure I'm adding to the conversation about the article, except to say that these concepts are no longer abstract to me. They're real. And they're in my world.
posted by ezust at 2:07 PM on February 19, 2015 [1 favorite]

Today on Fresh Air, Terry talks with virologist W. Ian Lipkin, technical advisor for the film Contagion, about the film, influenza, and emerging disease.
posted by j_curiouser at 4:19 PM on February 19, 2015

Shoot. ^^^ That is actually the guy talking with Ira Flatow on Science Friday, not Terry. Still good ;-)
posted by j_curiouser at 4:30 PM on February 19, 2015

We need to start thinking about how we approach medicine and health policy such that we're using evolution to our advantage and not to our detriment.

Think of all the great things we could accomplish if we weren't preoccupied with fighting about politics, and worked together for the long term.
posted by sneebler at 7:43 AM on February 21, 2015

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