The Omicron Hypothesis, Part 2

The Vaccine Wars Part XII

To think that a week ago, I thought I was working on a one-off article. This is going to take a few. And remember, I'm laying out facts, asking questions, and leaving open numerous hypotheses. The point is to get good investigation on track—particularly in the public sphere. Privately, I get the feeling there are more scientists who understand larger swaths of the story than will speak publicly. In fact, I'm almost daily hearing about those trying to shed greater light on important elements of the story, often trying to do so without attaching their own names. These are difficult times for honest scientists.

For anyone who wants to read or review Part 1:

The Omicron Hypothesis, Part 1

A quick summary of primary open hypotheses explored:

• Hypothesis 1: Omicron has been circulating widely for at least several months.

• Hypothesis 2: Omicron was genetically engineered—most likely by somebody in the same working group who engineered an mRNA vaccine to stop SARS-CoV-2.

Now, before we really get started again, some places (including those I mentioned in Part 1) where there is now a pandemic of the vaccinated.

• United Kingdom: Vaccinated twice as likely to have omicron than unvaccinated

  • Leaked Dept. of Health memo warns efficacy falls to zero against omicron.

  • The Imperial College of London finds an increasing affinity among the vaccinated for omicron relative to delta that increases with the number of doses taken.

• New South Wales, Australia

• Denmark data shows negative vaccine efficacy

• Oh, Canada!

  • Ontario: 95% of omicron cases in the vaccinated

  • Joel Smalley caught Alberta cooking the books to keep the vaccines from looking bad against omicron.

• Dec 13, 2021: The CDC says that 79% of early identified omicron infections are in vaccinated individuals.

• The vaccine manufacturers worry that their products do not protect against omicron

• Of course, New York bucks the trend. Really?

---

What Do The Genetic Sequences Tell Us?

The key aspect of omicron's genetic code to hone in on involves the nearly 4,000 nucleotides that makes up the coding for the spike protein. There, we see dozens of mutations that made a lot of people suspicious of the "variant" from the start. 

What is it those dirty, tinfoil-hat-wearing conspiracy theorists see?

Dr B. @P_J_Buckhaults

Spike is 3819 coding nucleotides. It has 33 NS and 1 S changes. The neighboring ORF3A-E-M-ORF6-ORF7A-ORF8-N-ORF10 genes have 4000 coding nucleotides. They have eight NS and three S changes. Spike is smaller and has four times the NS changes.

There is a lingo barrier to overcome here, so here is a basic genetics lesson:

• Proteins are the building blocks of the body.

• Amino acids are the building blocks of proteins.

• A codon is a three-nucleotide sequence that corresponds to an amino acid.

Note: There are 4*4*4 = 64 codons, three of which are "stop codons" that signal for termination of a protein synthesis process. That's where the amino acid chain that makes up a protein ends. Each of the other 61 codons encodes for one of 20 possible amino acids. There are more codons than amino acids because an amino acid can be generated using more than one codon sequence. Most amino acids can be produced by 2 or 4 distinct codons.

Naively, you might think that any mutation would be disastrous with respect to the process of producing the right amino acid sequence to create a protein. However, the several codons that produce a particular amino acid are often similar enough that changing one (or even two) of the nucleotides results in a synonymous codon (one that encodes for the same exact amino acid). Other times, non-synonymous codon mutations that do change an amino acid still don't greatly affect the overall shape or function of the generated protein.

Genetic Fact Check: If you're lucky, it doesn't matter when the condom breaks.

There was never going to be a better time, really. That joke is best made in an article that nakedly bumps up against the topic of ineffective prophylactic gene therapy products.

Thank you for tolerating all my "genetic humor." I'll be here all week.

The mutations in the codon sequence that change individual nucleotides are single nucleotide polymorphisms (SNPs) (like "snip", which makes the condom joke that much more cringeworthy). There is no one perfect answer to what proportion of these SNPs should be synonymous (S) vs. nonsynonymous (NS). That cannot be answered without wrapping a circumstantial model over the question (that one really isn't a condom joke). However, what we usually see is a 1:2 to 1:3 ratio (S to NS). That would mean 25% to 33% S mutations, sometimes called "silent" mutations. Let's roughly split the difference and use 30%.

In omicron we're seeing 3%. That does not look random! If you and I play 34 games of backgammon, and I have a probability of 30% to win each of them, the probability of me winning no more than a single game is about 1 in 11,867.

Here is a S vs. NS chart that includes "variants of concern" to drive the point home.

Tony VanDongen @tony_vandongen

Omicron does not have a natural origin. Its mutation properties place it in its own league when compared to all the natural variants. Red dot is Omicron. Blue dots are Variants of Concern (Delta etc.). Gray dots are other variants. Notice how isolated Omicron is.

If vague computational modeling on an ordinary binomial distribution doesn't convince you, let's zoom in on exactly what most of those NS codon mutations change, relative to the original SARS-CoV-2 (Wuhan) strain.

Tony VanDongen @tony_vandongen

Omicron has learned how to read!!! Of the 30 mutations in its spike gene, 24 have been characterized in scientific publications. Also, it borrowed defining mutations from alpha, beta, delta, eta, epsilon, iota and mu. Even though it was in hiding when these variants emerged.

This is where the Bayesians slap the frequentists in the face and declare, "Not a snowball's chance in Anthony Fauci's afterlife." Though omicron "developed" independently of the many other SARS-CoV-2 variants, it just sort of happens to share specific mutations associated with the exact characteristics of immune escape with all the many members of the variant alphabet.

Huh.

Do you think somebody wanted for omicron to escape all the antibody classes?

We'll come back to this point…

---

What's That Word, Again? Variant?

The media is strangely silent about omicron's genetic details. The term "variant" gets used, but is that terminology appropriate? It leaves people with the false impression that there is certainty (there isn't) or good reason to conclude (there isn't) that omicron diverged from the SARS-CoV-2 phylogenetic tree from some branch of the virus we now associate with Wuhan (I very much doubt it).

Ethical Skeptic ☀ @EthicalSkeptic

@THeNBLeNDr @tony_vandongen My analysis agrees with Tony, yes (see center lower chart panel). This is taking every single nucleotide and its entropy into account. No guessing, because genes do not lie.

Hypothesis 3 (the "don't call it a variant" hypothesis): Omicron did not emerge from the phylogenetic tree whose root is the first-sequenced Wuhan SARS-CoV-2 strain.

Alfred and I spent some time in the Bat CoV putting the following very professional-looking phylogenetic trees together. Sorry for my excellent handwriting. I'm definitely not vying for Dr. Mobeen Syed's job. But hopefully these make the competing hypotheses clear:

Scientists who have kept their sense of honesty intact in order to read words before the Ministry of Truth puts every last one of them (the words…or the scientists) in a blender have noted the weirdness surrounding the supposed closest SARS-CoV-2 relative, which is RaTG13. Fortunately, RaTG13 isn't showing up as a common name in baby registries yet, but it shares something in common with clean diapers: a lack of bacterial fingerprints you expect to find in poop.

Hopefully this makes apparent exactly why the WHO's rush to classify omicron as a "variant of concern" (which probably took place after 47 minutes of deliberation) should be viewed with a skeptical eye. Was that designation meant to throw the general public off the track of omicron's true origins?

Those who oversubscribe to Hanlon's razor might think authorities to be dim-witted. While that might not be wrong most of the time, assuming that such dim-wittedness implies that they are not also nefarious seems…bat CoV insane.

Focus on that area in the middle that is within the boundaries of both circles. Do you see it?

I'm gonna win a Nobel Prize for this. What really puts this theory-in-a-Venn-diagram over the top is that…it's intersectional.

---

When Circulating?

Recall the "Earlier Lab Leak Hypothesis".

The Earlier Lab Leak Hypothesis

I will now admit that I oversubscribed to the theory that SARS-CoV-2 was circulating longer than most people believed. While that's still very possible, I recognize the need to consider hypothesis interference. What if it was omicron that was circulating since early 2018?

The Ethical Skeptic thinks that an omicron ancestor may have been circulating prior to the official pandemic, conferring immunity as it spread:

Ethical Skeptic ☀ @EthicalSkeptic

@sdeddie71 @Josh_Ebner 1. Something conferred immunity globally prior to 2019 2. That something has to be very close to SARS-CoV-2 because we see that escape is a big issue 3. That something had to exist by 2018, be very transmissible, and be not as deadly... Omicron ancestor genetics fit this bill.

Now I wish that I'd been following TES twitter a little more closely. But as I've said, I was bored of variant porn until I began to suspect there was something interesting and different about omicron.

An interesting aspect of an "earlier omicron hypothesis" is that it might explain why so much of the Asia-Pacific rim saw lower death from COVID-19 beyond any reasonable interpretation of variables such as comorbidity rates, dirty smokers, super-authoritarian-Chinese lockdowns, Asians of "act as one like grains of wheat, swaying together in the wind", and slightly higher mask adherence rates.

Is this why the Kunlangeta running Australia and New Zealand had to keep those nations so completely locked down? So that it wouldn't be apparent that the Omicron-CoV-2018 hadn't already conferred significant immunity to the only substantial populations of Euro-ancestry in the region?

---

Since I'm sorting out so much other research at the moment, I'm going to go ahead and stop here. There are a tremendous number of pieces to cover, and some of them go all the way back to 2013. We're going to talk entropy, Wuhan CoV research, Ralph Baric, swarms, viral latency, and vaccine target painting. This is going to be fun, kiddos. How could you not have fun talking about Ralph Baric? He's like what would happen if an out-of-control centralized grant and patent system were run as an America's Mad Scientist Idol competition.

Stay Tuned…