Monkeypox will evolve much faster than you expect

I couldn’t help but steal some stock footage

An argument you will encounter a lot, is that DNA viruses mutate at about 1% of the pace of RNA viruses and thus monkeypox is not going to undergo the sort of rapid adaptation to our species that SARS-COV-2 went through. And although it’s true that RNA viruses mutate more rapidly through single point mutations than DNA viruses do, that’s the sort of simplification that’s going to lead people to underestimate what this virus can do.

To start with, observed mutation rates will depend not just on the intrinsic propensity of RNA to undergo errors, but also on how well adjusted the genetic material already is to our species. When SARS-COV-2 first emerged, its spike protein was already well adopted to our ACE2 receptor and in an immunologically naive population we witnessed very few mutations for the first year or so. After all, the mutations that took place would generally not have a fitness advantage and thus we never really observed them in more than a handful of isolated cases.

It’s only once a lot of people had some degree of immunity, that we began to see variants emerge. The observed rate at which the spike protein changes depends on the evolutionary pressure it’s under to change. As the first version was already at a local optimum, it didn’t really change until there was widespread immunity.

But as the evidence piles up, there are more reasons to expect that we’re underestimating how rapidly this virus will change. SARS-COV-2 appears capable of giving rise to new variants that are a product of recombination between other variants, but it’s a very rare phenomenon. On the other hand, that doesn’t seem to be the case for monkeypox. Two strains of monkeypox that infect the same individual (which is already happening surprisingly often) will happily recombine to give rise to a new variant.

Scientists looked at a few hundred monkeypox genomes from patients and already found eight examples of recombinants caused by coinfection by divergent strains. Specifically, they looked at 415 sequences collected between January and July:

Here we report the first evidence of recombination of monkeypox genome in natural transmission by analyzing six tandem repeats (TRs) among 415 sequences collected between January to July 2022

And what they found was as following:

Poxvirus recombination between two co-infecting parental viruses generates genetic diversity (Ball, 1987; Ball, 1995, Evans et al., 1988; Sasani, et al, 2018). Monkeypox recombination in natural infection has not been reported to date. Using TR polymorphism, we identified 8 genomes with recombinant crossovers (Figure 2). Case FVG-ITA-01 (ON755039) in Italy may be generated from parental sequences from the group I and M. Case VIDRL01 (ON631963) in Australia comes from parental sequence of the group M and U (Figure 1E), as well as six cases of Slovenia cases (ON838178, ON631241, ON609725, ON754985, ON754986, ON754987). This is the first report of recombination of monkeypox in natural transmission to our knowledge.

I really can’t sufficiently emphasize how significant this finding is. They looked at just 415 sequences and found eight cases where two lineages showed up in the same dude and gave birth to a new version. This means that recombination is many orders of magnitude more common per infection for this virus, than it is for SARS-COV-2.

It also means that mass gatherings of people from around the world are much more relevant when it comes to monkeypox, than they were for SARS-COV-2. When people hold a gay festival, where tens of thousands of gay men from all sorts of cities across a continent gather together, monkeypox gets an opportunity to take the best improvements it could come up with in those cities and put many of those improvements together in one new genome.

And so although I’m pretty sure it’s hopeless, I’m going to tell you once again that the Southern Decadence festival that’s going to be held in New Orleans in a few days is a very bad idea.

You also need to realize that this virus is now getting opportunities to improve itself that smallpox didn’t really get. There was no way for infected Aztec warriors to step into an airplane after their population was decimated by smallpox, step out in Paris, sleep with a local infected woman and give rise to a new version of smallpox that inherited the most virulent genes of both strains. The people who lived in the last rural pockets of the world where this virus survived when we began eradicating it didn’t get the opportunity to jump on an airplane and give birth to recombinants by meeting up with other rural African villagers either.

We created a unique new situation for this virus through the airline industry, where populations that would normally be isolated from each other can now regularly interact again and give this virus the chance to produce recombinations of itself.

The biggest wildcard I don’t have an answer to is: Can vaccinia virus recombine itself with monkeypox? It seems we’re going to be using live replicating vaccinia virus in some people in an effort to protect them against monkeypox. If we get a situation where monkeypox gets to exchange genes with the vaccinia virus, this could all get very interesting very fast.

This is not a trivial question. British scientists raised the scenario a while ago of SARS-COV-2 inheriting a polymerase gene from influenza and giving rise to a new very virulent variant. That seems rather far-fetched and hypothetical to me, but if you look at how often monkeypox strains apparently manage to recombine with each other to give birth to new strains when they have the luck of infecting one person simultaneously, recombination between vaccinia and monkeypox looks far more plausible to me.

I’m not going to change this, you my dear reader are not going to change this either. I’m not going to earn a quick buck by writing about it either. I could write an essay every day, I could even have it go viral, but men in New Orleans will still be publicly screwing each other in broad daylight a few days from now. So you might be wondering: Why do I even bother?

The honest answer, is that it’s all entertaining to watch. I can’t be the only person on the planet who is genuinely intrigued by medical horror, government incompetence and evolutionary dynamics. And this story has it all. Human incompetence and the tendency for ambitious hypersocial people of relatively modest intelligence to dominate government bureaucracies in modern Western society is giving birth as we speak to a new version of smallpox, one of the most deadly viruses in human history.

They’re not really trying to eradicate this virus. We now know what it looks like when your government is very worried about a virus: You have troops marching through the streets and the border is physically blocked, they dumped piles of sand on the roads leading into Belgium here.

No, they’re “managing” this crisis. To some degree they have already thrown in the towel, accepting that this virus will still be infecting people months from now. They’re definitely not looking ahead. “How do we avoid offending People of Buttsex?” is a more urgent question to them than “how is an orthopox virus going to adapt as it spreads uncontrollably from person to person through the population?”

9 Comments

  1. New Orleans takes place the 1st of September the third week in September all those infected in New Orleans will have the opportunity to spread monkeypox to a new generation of victims those will then spread it to a third level who will become symptomatic by mid and late October just in time to shut the country down and demand mail-in ballots. There plan is working well and on schedule

  2. “It seems we’re going to be using live replicating vaccinia virus in some people in an effort to protect them against monkeypox.”

    Is that just your supposition based on what would/will happen should monkeypox break out in a big way and Jynneos proves inadequate, or are you referencing something specific you’ve come across?

    • I think he means that people who have been vaxxed for small pox, or by using the small pox vaccine itself as monkey pox rolls out. That is my assumption anyway.

  3. Reading your articles often strikes a philosophical note in me. I can’t help but feel like world affairs exhibit a cyclical nature to them. It’s kind of like the saying, “history doesn’t repeat itself, but it does rhyme.” Circumstances seem to go back and forth between being good and bad. There doesn’t seem to be any stability at all. Learning to live life, physically and especially mentally, under forever changing circumstances and learning to detach oneself from both happiness and unhappiness seems to be the best thing one can learn to do.

  4. “the tendency for ambitious hypersocial people of relatively modest intelligence to dominate government bureaucracies in modern Western society”
    You’ve said that loads of times but it is still funny.
    I think they are also very present in the media and in education. People of modest intelligence, I mean.
    Lots of clever people are losers, they can’t fit in.

  5. I don’t think those in positions of power are of middling intelligence, I think they are high on intellect, and low on wisdom. You can be very clever (the sort of person who can read complex legal documents and understand them, and write similar for example) and yet you can also be the sort of person who falls for the 419 scam, one that a far lower intellect (but wiser) person would spot a mile off. Modern society generally selects for intellect via the education system, it does nothing to select for wisdom. And yet wisdom (the ability sniff when something is wrong, when something doesn’t add up, or to see flaws in plans that on paper look great) is crucial for good decision making processes. But no-one ever considers it necessary in potential decision makers.

    • Because ass-kissers are rewarded with management and leadership positions. If you’re relatively intelligent and an ass-kisser, you’re sure to do well in our society. Companies, universities, and governments don’t want bold thinkers who are willing to carve a better path for the masses; they want “yes men” who will carry out orders from their superiors, no matter how idiotic the orders seem to be.

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