Sunday, June 14, 2020

The Great Pause Week 13: Wisdom from a Mouse


mouse

Hi there, it’s your friendly neighborhood lab mouse here. Just to recap for those just joining this conversation, my dad was one of the first lab animals to be genetically engineered to receive SARS-CoV-2, but the scientists doing the engineering were sloppy and did not anticipate the human epigenome they were also transplanting, resulting in Pop having an Ah-ha! moment post-op and bugging out of the lab before he got sliced and diced for science.

I’ve had a few more observations since I last wrote, which are what bring me back this week. Thanks for the space, Albert. Firstly, I notice that most humans are corona-fatigued, bored staying at home, and just want to get back to a “normal” life. While I understand that, I might have to point out that what y’all called normal was pretty unsustainable to begin with, and a reckoning was due. You can try to get ‘normal’ back, but even if you recovered that kind of lifestyle again, it would be short-lived.

Maybe you just don’t fully grasp zoonosis. Viruses are so simple that they don’t need their own body to survive; just short snippets of code. They have circadian rhythms like frogs, crickets, or seven-year locusts — periods of dormancy and rounds of travel. Some viruses that have lived within our mammalian bodies’ genome for millions of years wake up whenever diseases attack us and they stimulate the response that sends special killer cells into the bloodstream to hunt and attack disease cells. Others only wake up during pregnancy to supply a placenta.

Some kinds of viruses don’t need rhythmic cycles. They don’t need a physical form. These disembodied fragments are called transposable elements, or transposons. They are mobile genetic wraiths — sequences of code that physically move in and out of chromosomes. They are sometimes called “jumping genes.” Around 8% of the human genome is made up of viruses, but nearly 50% is made of transposons. Biologist Ben Callif says that “Humans are basically just big piles of viral-like sequences.”

For many years, y’all did not consider these very small parts very important, except perhaps as carriers of disease. You still don’t seem to know they are essential threads in the web of life, on land and in the sea. They are many times more numerous than more complex life forms. 

A pint of crystal clear seawater contains 2 billion viruses. There are 15 times more viruses, for instance, in the ocean than all other types of marine life combined. To count them, you would have to use 30 zeros. If you laid them end to end, it would make a string two hundred times finer than the most delicate spider string, and it would extend out 200 million light-years, passing along the way 40 galaxies as massive as our own Milky Way.

When you add to those viruses the ones floating in air, resting on land, or deep underground, you’ll have to add another zero. You just multiplied the previous number by ten. There are over ten million times more viruses on Earth than there are stars in our entire universe. A single virus, traveling in the wake of a comet, may have brought life to Earth.

Your genome, which can fit into one trillionth of a gram of nucleic acid (as it does in every tissue cell in your body), is 99% identical to a chimpanzee’s. So, technically, it’s a blueprint for building a chimp, with a few minor alterations. One of those lets it do things no monkey would ever do, like drain swamps or cut down whole forests. Your hot-rod monkey has released viruses that should never have been released.

We mice have learned to make our peace with viruses. In the first place, we have been around for at least twice as long as humans have, existing in this form for some 5 million years. Mice and men’s common ancestor looks a lot more like us than like you. But we can still be friends. 

We mice might not even be living in the Western Hemisphere, Pacific islands or tropical Africa had we not voyaged with you. Now mousekind exists pretty much everywhere, thanks to you, and to our ability to genetically adapt to our environment.

The problem is you hairless apes just couldn’t adapt. You had all that fossil sunlight you could pump from the ground and burn to make steel and run cars, and you thought everything belonged to you. You kept having babies even after you knew such a large population could not be sustained with the resources of a single planet. You just figured you would get more planets, or something, I don’t know.
 
Maybe even the collaboration with horses might have been too much horsepower for monkeys, but what you did when you started breaking down the rainforests, the mountaintops, the oceans, and every nook and cranny is, you broke up a lot of very stable and long-term symbiotic connections between viruses and their reservoirs. 

Viruses reproduce within particular hosts, their reservoirs, so they need to remain in places where those hosts live in order to reproduce. It does a virus no good to kill its host, so most natural reservoirs like birds, mice and bats have developed a tolerance. 

Since they have no arms or legs, viruses can only move by blowing on the wind, floating through liquid, or sticking to a surface where they rub off on something passing by. Some years ago a particular virus had a type of fox-bat found in northeastern Australia as its reservoir. At some point, a bat bit a horse and the virus jumped. When it successfully went from hacking the bat’s genetic code to hacking the horse’s genetic code, it was thereafter able to travel wherever the horse went and was not stuck living in a cave or a tree. Later, this same virus jumped again from horses to humans and got called Hendra virus.

Whenever a virus successfully migrates from one reservoir to another, it is called “spillover.” In this example, Hendra virus also infected dogs but was unable to hack their genetic code the way it had bats, horses and humans, so it did not spill over into dogs.

From where do these viruses jump? They jump from animals in which they have long abided, found safety, and occasionally gotten stuck. They jump, that is, from their reservoir hosts. And which animals are those? Some kinds are more deeply implicated than others as reservoirs of the zoonotic viruses that jump into humans. Hantaviruses jump from rodents. Lassa too jumps from rodents. Yellow fever virus jumps from monkeys. Monkeypox, despite its name, seems to jump mainly from squirrels. Herpes B jumps from macaques. The influenzas jump from wild birds into domestic poultry and then into people, sometimes after a transformative stopover in pigs. Measles may originally have jumped into us from domesticated sheep and goats. HIV-1 has jumped our way from chimpanzees. So there’s a certain diversity of origins. But a large fraction of all the scary new viruses I’ve mentioned so far, as well as others I haven’t mentioned, come jumping at us from bats. Hendra: from bats. Marburg: from bats. SARS-CoV: from bats. Rabies, when it jumps into people, comes usually from domestic dogs — because mad dogs get more opportunities than mad wildlife to sink their teeth into humans — but bats are among its chief reservoirs. Duvenhage, a rabies cousin, jumps to humans from bats. Kyasanur Forest virus is vectored by ticks, which carry it to people from several kinds of wildlife, including bats. Ebola, very possibly: from bats. Menangle: from bats. Tioman: from bats. Melaka: from bats. Australian bat lyssavirus, it may not surprise you to learn, has its reservoir in Australian bats. And though the list already is long, a little bit menacing, and in need of calm explanation, it wouldn’t be complete without adding Nipah, one of the more dramatic RNA viruses to emerge within recent decades, which leaps into pigs and via them into humans: from bats.

— David Quammen, Spillover: Animal Infections and the Next Human Pandemic (pp. 313–314). W. W. Norton & Company. Kindle Edition.

Whenever a virus successfully hacks a new genome, several outcomes become possible. Sometimes it is better than the previous reservoir, so the new home becomes an amplifier of the virus. Sometimes the association is so lethal it destroys the reservoir, taking the virus with it. 

Whenever a spillover happens, the genetic code of the virus diverges 30 to 40 percent from the original to adapt to the ecologic niche of its new reservoir. Because of this, it cannot “spill back,” or return to its original reservoir once it has made the leap, although the original virus may still keep some population in the original.

The original reservoir host of ebolavirus was chimpanzees. It tried spilling to gorillas but it killed whole tribes so gorillas were a “dead-end host,” as distinct from “reservoir host,” for ebolaviruses. Spilling over into humans, it had an amplifier, although the infection was fatal to its new host more than half the time. Humans were mobile. Since one human could infect another, through direct contact with bodily fluids, the disease spread in Equatorial Africa, but because it was so lethal, it couldn’t keep going through many successive cases or cover great distances quickly. Isolation wards, masks, gloves, and disposable needles are adequate to end outbreaks.

A different example us eastern equine encephalitis. It’s been around since 1831 when Massachusetts farmers discovered previously healthy horses lying on their flanks, moving their legs in swimming motions and then expiring, violently. Now, with sprawling suburbs encroaching on swamps and climate change’s milder winters and intense summers, EEE-carrying mosquitoes are humming beyond Massachusetts, to Connecticut, Rhode Island, New Jersey, and Michigan. The case fatality rate is 40 percent in humans. 

David Quammen says, “Every spillover is like a sweepstakes ticket, bought by the pathogen, for the prize of a new and more grandiose existence. It’s a long-shot chance to transcend the dead end. To go where it hasn’t gone and be what it hasn’t been. Sometimes the bettor wins big.” Other times, it is the end of their line.

For centuries, perhaps millennia, the EEE virus had a symbiotic relationship with migratory songbirds. They were immune to it, but in swampland they could be bitten by a mosquito, the Culiseta melanura, that had a limited flight range of about two miles and fed almost exclusively on bird blood. The birds were the reservoir and the mosquito was a virus vector that kept it moving from bird to bird and reproducing. 

Sometimes, on rare occasions, the infected birds were bitten by Coquillettidia perturbans, a mosquito that takes blood meals from both birds and mammals. That kind of mosquito is a “bridging vector.” It passed EEE to horses, probably some mice, and later humans. But once the virus left the swamps and reached these mammals, it killed them. That’s a dead end. EEE cannot be transmitted from horse to horse or human to human without a bridging vector. It did not spill over. 

Viruses do not have any way to travel other than by their hosts. If they spill over from a bat to a mosquito they might travel no more than a few miles and never leave that local ecology. But sometimes they get lucky and spill over into a horse or a human and find they can transfer to other horses or humans. As a horse, it can travel much more than a swamp mosquito but still less than a human, with a few exceptions. As a human — or as an exceptional horse like a racehorse or polo pony — it could be in China one day, Europe the next, and the United States the day after that. Traveling in water droplets from respiration or flatulence, it can jump from host to host everywhere it goes, it can go nearly anywhere, including around the Moon, as it did on Apollo 13.

So in a way, spilling over from a bat to a human-like SARS-CoV-2 is like winning a jackpot. This little spikeball might have spent 10,000 years in that same cave in China. How boring was that? In just six months it jumped to every corner of the world and is still doubling the size of its reservoir every few weeks. Do you think CoV-2 is likely to give that up any time soon and just mutate into something harmless? I doubt it.

You can go ahead and keep looking for a vaccine, and who knows, maybe you will win the lottery. But that’s a long shot. RNA viruses such as coronavirus mutate too fast to be vaccinated against.

What really needs to happen is you need to learn to stop draining swamps, cutting down rainforests, removing mountaintops, mining the oceans, and eating every bat from every nook and cranny of any old cave. Seriously. You need to control the size of your population and get a handle on its appetites. If you want to solve problems like viral pandemics and climate chaos, you will need to learn to attack causes, not symptoms. 

Because if you think this coronavirus is bad, I can assure you there are much worse still out there, just waiting for a chance to leap. The cause of this pandemic, and probably the next, is human spillover into viral habitats.


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I made a correction to the count in the title this week. I went into corona lockdown March 15, and the first journal entry, titled The Great Pause, was published March 22. The Great Pause Week One was posted March 29, which was actually the end of week two. To correct for these dates, this post is skipping 12 and going straight to week 13.

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