Everyone has some opinion on the lab experiments where mice are infected with synthetic hybrids of different SARS-COV-2 variants. I’m not too fond of such experiments, but lack of scientific knowledge is causing people to ignore the far more dangerous experiments performed with SARS-COV-2 that happen outside of the lab. There could be extremely dangerous experiments happening with SARS-COV-2 right now in a hospital near you.
There is a weapon of mass destruction known as Molnupiravir, which attempts to treat patients by causing mutation accumulation. Increase the mutation rate of SARS-COV-2 enough and the viral infection becomes less “fit”, making it easier for the body to fight off the virus. This is the theory and there’s no good evidence it even works, but the problem should be obvious: There’s a difficult to quantify risk that you would give rise to new variants. And because you are artificially inducing mutations in a manner very different from known mechanisms through which this virus mutates, you could arrive at novel positions on the fitness landscape that would be neigh impossible for natural selection to arrive at on timescales relevant to human civilization.
There’s a really good thread on Molnupiravir you can find on Twitter here:
But since this thread was posted, we now have the first example, of a rapidly spreading novel variant of SARS-COV-2, that came into existence due to molnupiravir. We know it was caused by molnupiravir, because its mutation profile fits exactly the sort of mutations molnupiravir induces, mutations that are rarely induced through natural evolution. This is a product of human tinkering with the genome, by administering medication to immunocompromised hosts that was specifically designed to induce mutations in SARS-COV-2.
What has happened here is worse than a second lab leak of one of these spliced together versions of SARS-COV-2 would be. SARS-COV-2 will naturally give rise to hybrid strains, this is inevitable. What’s not inevitable however, is a saltation of non-Spike genes. That doesn’t normally happen, because there’s no strong selection operating on those genes.
Although there may be versions that would work much better, you miss a viable path through the intermediate steps, as those don’t carry a fitness benefit. But with Molnupiravir, this doesn’t matter: You give this medication, the virus ends up with a large bunch of mutations in ORF1a or some other non-spike gene and it can stumble upon a different viable position in the fitness landscape for those genes by accident.
Although ORF1a and other genes will incur mutations from time to time, you won’t see a large pile of mutations in one individual viral particle show up all at once. You can check this by looking at the studies observing persistent infections: Those persistent infections do accumulate mutations, but one at a time, not a bunch of mutations all at once.
With medication like Molnupiravir, this does happen: A single particle can accumulate a bunch of mutations at once, which then allows this virus to teleport onto a different random position on the fitness landscape. Most of the time it will be teleported onto the ocean and drown, but sometimes it will be placed on another island. Natural mutation on the other hand can be thought of as the virus moving around on an island: If it moves away too far from its starting position it simply drowns.
People are already trying to downplay what happened:
Beyond the remarkable speed with which these mutations appeared, they are not at all the convergent mutations we have been seeing in recent saltations. I believe that @ryhisner has a plausible explanation for this. “Molnupiravir works by preferentially causing transition mutations, especially C->T and G->A mutations. 41/42 nuc mutations here are transitions, and 37/42 are C->T or G->A.” Molnupiravir can be prescribed in the ACT, so this is a possibility.
To my knowledge, this is the most divergent BA.2-derived non-recombinant variant to have been observed in multiple patients so far. If Molnupiravir selection has contributed to the emergence of these mutations, then I’d expect this will not be a very fit variant, but it is still notable that it has been found in 9 different patients so far.
The author who wrote this seems to be forgetting that the fitness of this variant has to meet a minimum threshold, for him to become aware of its existence in the first place! Sure, most of the monsters born from Molnupiravir will have reduced fitness, but you will never observe those in the first place! The fact that this variant has infected at least 9 different people within days, suggests it must have sufficient fitness to spread effectively from person to person. It will now undergo natural selection: It will observe the island on the fitness landscape it found itself on and start climbing to the highest mountain.
Never before have we seen a BA.2 derived variant that has evolved so far away from its ancestor. And remember: We did this ourselves. The most divergent human to human spreading BA.2 descendant is man-made. This was not mother nature, this was entirely a product of human beings forcing this virus to undergo mutations that would never accumulate spontaneously during its replication cycle.
Virulence of the Omicron family was reduced because of non-Spike mutations. The evolution since then has mostly happened in Spike, because that’s where our antibody response is encouraging the emergence of novel versions of Spike. But this monster, this is something entirely different. This has a bunch of novel never before seen mutations, piled up in genes that have no strong incentive to mutate. We have no idea what it does: Whether this will push up virulence or push it down.
I will without a doubt be accused of fear-mongering by the usual suspects, who wish to sleep comfortably at night by blinding themselves to tail-risks. But the simple fact is as following: You haven’t got the slightest idea how you’re going to quantify the risk associated with what has happened here. It’s the equivalent of laughing at me, because you snorted a line of cocaine and didn’t drop dead even though I warned you it could be contaminated with fentanyl.
But allow me to illustrate to you again, the insanity of what humans have allowed to happen here:
This implies that from approximately 8/29 to 9/11, the genome accumulated 35 NT (24 AA) mutations. The Schwessinger lab have confirmed that no closer ancestral sequences have been recovered, even when including sequences not yet publicly available. SARS-CoV-2 sequencing rates in the ACT during September (when these samples were collected) ranged from 8-14% of all notified cases (PCR- and RAT-based diagnosis); thus, if intermediary sequences were present in the population there is a high probability that at least some would have been sequenced. Beyond the remarkable speed with which these mutations appeared, they are not at all the convergent mutations we have been seeing in recent saltations.
Do me a favor, look through the literature, through all the available evidence, find me a case of a SARS-COV-2 variant fit enough to spread from person to person accumulating 35 nucleotide mutations in a two-week period. It doesn’t happen. It’s unprecedented.
It’s perfectly possible this variant doesn’t have a fitness advantage, but repeat this experiment often enough and you’ll give birth to one that does. Out of its seven Spike mutations, six have never been observed before.
The Molnupiravir is honestly a more frightening experiment than the vaccines, but it’s so self-evidently stupid and reckless, that nobody really bothers to talk about it. The vaccines are subject to a Streissand effect: Point out the risk and you’re banned from Twitter and polite society, so everyone talks about it. Molnupiravir is dangerous, but it’s completely obvious and indisputable so nobody really pays attention to what’s going on.
The best way to think about it is to imagine that we now have thousands of Chinese virus labs around the globe, where people use weird tools to give birth to strange new viruses, every once in a while stumbling upon some new abomination that escapes from the lab. There is no way to justify this drug, it’s a bizarre tail risk we inflicted upon ourselves, for reasons entirely unclear to me.
We have some vague clue what it’s doing to SARS-COV-2, because people constantly sequence this virus. This is not the first Molnupiravir variant, it’s just the first one seen spreading from person to person. But you have to keep in mind, that Molnupiravir can do to other viruses what it does to SARS-COV-2. It could take any other respiratory virus and teleport it across the fitness landscape. It’s an insane unprecedented global experiment, it’s the first time we’re trying to fight a virus by constantly randomly mutating it. They need to ban this drug right now and hope that we lucked out.