Ivermectin is the red pill

These days if you put it to a follower of the mainstream that lockdowns, masks and jabs did far more harm than good they may even agree. But you can be sure they’ll justify the child cruelty, deliberately-induced mob hysteria and unquestioned withdrawal of our most basic human rights with some argument that we had to do something to address the terrible scourge of covid.

It was such a crazy time, heh!

But tell them a treatment for covid was available from day 1 that was well studied, widely available, extremely safe and cheap but the authorities went to extraordinary lengths to stop it being used and they will have to change the subject urgently. Or wake up.

There is no way for even the most ardent apologist for tyranny to justify the deliberate suppression of a treatment that could have ended “the pandemic”. No conclusion is possible except that the authorities are indeed malign, and were willing to sacrifice millions of lives - along with our claimed principles and freedoms - for some purpose that served their interests, but left patients with ventilation and midazolam as their only options.

The story of ivermectin is properly told by others better qualified. But my summary is:

• As much as you can say that any drug works, ivermectin works against covid. The only qualification I can see is to what extent the benefits extend to mortality, as RCTs seem underpowered to tell this. But as its pretty clear it has some effect on the disease, you’d have to say an effect on mortality is expected. And nobody can dispute, with integrity, that it seems extremely safe.

• It is absolutely indisputable that the authorities have lied and cheated to prevent ivermectin being used. This includes the simple expedient of writing negative conclusions over positive results (eg the rewriting of the WHO guidelines, for which Tess Lawrie famously called out Andrew Hill) and conducting trials, effectively sponsored by pharma, apparently rigged to show no benefit - see below. One of my favorites is the simple lie that ivermectin overdoses were backing up ERs - since shown to be pure fabrication. The title of the article has changed but this disinformation is still out there:

• The mainstream medicine / pharma / media complex carried out its usual crushing of careers of anyone who dared speak the truth about it. You can add to this the nauseating spectacle of pharmacists who happily doled out fentanyl refusing to fill valid ivermectin prescriptions on “ethical” grounds.

For the detailed story, I recommend The War on Ivermectin by Pierre Kory.

But why, your mainstreamer may ask, if they haven’t already gone quiet, would our authorities do this??

There’s (at least) one nice simple answer: the covid jabs were able to circumvent most of the requirements for proper research and trials - already fairly badly undermined, its true - and get all sorts of other advantages, by qualifying for an Emergency Use Authorization (EUA).

And you can only get an EUA if there is no existing recommended treatment for the condition in question.

So they had to trash anything that could get a recommendation, or the whole mRNA vaccination project would have been jeopardised.

They had to trash it whether it worked or not.

The PRINCIPLE trial was already a smoking gun

Pharma companies have two key competencies: bribing payers (doctors and governments); and rigging clinical trials. Of course they used both these superpowers to the max throughout covid, and against ivermectin, but we’re going to focus here on the trials.

There are innumerable ways, if you are in control of a clinical trial, that you can tweak things in the direction of the outcome you want. Choose the right thing to measure, the right people to recruit, the right times to test, the right dosing regimen. A lot of this is “legit” - even before you get into choosing which data to publish, and outright cheating like unblinding and so forth.

These tactics are usually used to make a poor drug candidate look like it works. But they can also be used - a lot more easily, actually - to make something that works look like it doesn’t.

This dichotomy is neatly shown in two trials of covid antivirals: one for the pharma-sponsored molnupiravir, a patented drug costing $700 for a 5 day course, and the other for ivermectin costing next to nothing.

It so happened that the same investigator ran both these trials. As shown in the table below, despite being expected to work in basically the same way, trials of the two drugs made very different choices about trial population, the time at which treatment was given, and other key parameters.

source

You may not be surprised to learn that the design choices for ivermectin tend to make it a lot harder to show a benefit - while those made for the pharma-patented product seem keenly tailored to maximise any positive effect.

For example, patients were recruited to the ivermectin trial up to 14 days after symptoms - far too late to expect a benefit - while the latest time for molnupiravir was 5 days. Subjects were specifically told to take ivermectin on an empty stomach - although this is known to reduce efficacy.

Pierre Kory has, as you would expect, an excellent write up of this trial and its chicanery, including the startling fact that, despite their apparent efforts to load the dice against ivermectin, many of the results are actually positive and significant. For example, see this slew of findings showing ivermectin alleviating the symptoms of covid:

Seems inconvenient in a study that concludes:

Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted.

However the ‘researchers’ managed to alleviate any awkwardness with the simple expedient of sticking this data - along with tiresome details of how they designed the trial and so forth - in an a supplementary annex, linked on the web page. Huh.

You don’t need to be certain ivermectin works to be certain the establishment is lying about it

To summarise my view of ivermectin: as someone with a career in this field I am, in principle, sceptical of claims for efficacy (or safety) of any drug. It’s just so incredibly difficult to attribute causality, even if the trials are honest. The evidence I’ve seen seems pretty much as reliable as one could hope for, and if I felt threatened by covid I’d definitely take ivermectin. Its important to note that the evidence favouring ivermectin comes from studies that do not have anything remotely like the conflict of interest in any trial of a patented product - which significantly increases the confidence that it was generated in good faith. But my principled uncertainty applies to ivermectin, as it does to any drug.

However what I am absolutely certain about is that the authorities have deliberately lied to make it seem ivermectin doesn’t work, and to prevent its use - even though there is significant evidence to suggest it works, it is clearly safe, and patients had no viable alternative. The medical establishment has broken all rules of scientific integrity, and they have been caught going to extreme lengths to suppress a drug that could have prevented “the pandemic”.

The PRINCIPLE trial is one of the best pieces of evidence for this - possibly the clearest smoking gun of the whole covid saga, and its right there in black and white.

Or it was..

Now they have deleted the annex that gave the game away

When the story of PRINCIPLE broke, along with all the apparently positive results that had been buried in the annex, I went to the journal site to check it was true. Sure enough, all the apparently positive results I’d seen were there in a large pdf of supplementary material.

Being of suspicious and cautious nature I habitually take personal copies of material I feel may be useful for, I don’t know, some kind of second Nuremburg or something.. ..so I downloaded a copy of the pdf - amounting to ~400 pages and 18MB.

Which is a good job because Today I Learned (from this zerohedge article) the annex is nowhere to be seen on the journal page. Where once there were two linked pdfs, if I recall correctly, now there is only one - but it has been duplicated. Presumably to make it appear as if there are two pdfs.

Now why would they do that?

Anyone who wants a copy do let me know and we can sort something out..

“Bitcoin has no intrinsic value”

”Bitcoin isn’t backed by anything”

“Bitcoin doesn’t generate any returns”

“Bitcoin’s value is from pure speculation”

“Bitcoin is a bubble”

Those of us who have been following bitcoin for a while will feel a rosy glow of nostalgia to hear the mainstream economic establishment again wheeling out these facile tropes in their increasingly desperate-looking attempts to convince the plebs that bitcoin is just a Ponzi scheme that will collapse any day, and to instead trust their banking system which has never tried to screw them.

But the Rubicon has been crossed now. The Trojan Horse has entered and the gates of the citadel locked behind. With the approval of the US spot bitcoin ETFs - in particular by BlackRock, who are (one imagines) at the absolute power centre of Wall Street - humanity has passed, almost silently, over the event horizon beyond which the gravitational attraction of bitcoin is probably inescapable.

And a large part of the reason for this is that the mainstream quotes above are essentially correct. Their authors think they mean bitcoin will fail, but anyone who thinks objectively can see that the opposite is true - and the implications for humanity are huge.

The essence of these critiques is that the price of bitcoin is determined by pure speculation, and not connected to any physical or economic reality. This is exactly right. If mainstream economists did what they are supposed to, and actually consider what it means, they’d quickly realize we are in uncharted territory. Because no such asset has ever existed before.

To be specific: bitcoin is the first and only asset whose supply is not affected by its price. This means it is not subject to the natural constraint on all assets humanity has ever known, whose supply will increase in response to price rises, thereby choking them off.

Without that constraint, the known laws of supply and demand just don’t apply.

So what does determine bitcoin’s ultimate “fair value”? This post shows how, without any physical or economic reality to limit bitcoin’s price, it will be driven up by a positive feedback loop of self-fulfilling expectation that only stops when the entire world is “all in”. At that point, everyone still thinks the price of bitcoin is going up, but they don’t buy any more because they have nothing left to buy it with.

If this happens - and after many years pondering this question, I can’t see anything likely to stop it - it’ll pretty much be The End of the World As We Know It.

All assets before bitcoin have prices connected to physical or economic reality

Before bitcoin, anything you could own - stocks, bonds, gold, $$$, property, commodities, cans of beans, ammo - has some notion of value that is connected to activities in the real world.

For things you can inhabit, eat, burn or shoot, this connection is obvious - they will be valued in the market according to how much people want to inhabit, eat, burn or shoot them, and how hard it is to make more of them.

Things get more interesting with gold. Industrial demand for gold cannot possibly explain its market price, which clearly resides in something else: its utility as a store of value per se. This begins part of the logical circuit we will see in bitcoin: the higher the price of gold, the better it has performed as a store of value.. ..so the more highly demanded it will be for people seeking a store of value and the higher its price.. All else equal this loop would lead to a price that spirals off towards infinity.

But the price of gold is not infinity - for the same reason the price of tulips and south sea stock and any other (traditional) asset is not infinity: supply responds to price. When the price of something goes up, it increases the returns available to anyone who produces more of it - so more is produced. When this additional supply comes to market, it suppresses the price.

That economic tether is present for all assets before bitcoin. Known gold deposits are everywhere - but they are too costly to mine at current prices. If the gold price goes up, they become economic to extract so they will be extracted. We have only mined a vanishingly small proportion of the gold available even in the Earth’s crust - let alone that buried deeper, or in asteroids. So its easy to see that the price of gold will always be connected to, and limited by, the cost of generating new gold.

When you look for it, this connection between price and supply is present everywhere. If a stock price increases it incentivizes more stock to be issued, either of that same company or of new entrants deploying capital in its market. If interest rates rise it incentivizes more supply of loans (bonds) by creditors. If land prices rise it incentivizes more development, regeneration, reclamation or even ultimately planetary exploration.

This connection is deeply engrained in our consciousness, and implicitly determines our initial attitude to anything you can buy (or sell). It is the reason all speculative bubbles have ultimately burst.

All bubbles until bitcoin, that is - because for bitcoin, that connection simply does not exist.

A brief introduction to Bitcoin supply

Everyone probably knows by now that the bitcoin supply is “fixed”. That’s not to say there will never be any new bitcoins produced, but the schedule of their production is predetermined. There are currently about 19 million in circulation. After April 2024’s “halving” event, the rate of production will fall from ~900 per day to ~450 per day. Four years later it will halve again, and so on. In the year 2140 the last fraction of a bitcoin will be produced, for a grand total of 21 million.

The precise schedule doesn’t matter. The key fact is that it is completely* independent of price.

(*for nit-pickers, there is technically a way that price changes can have a slight effect on how fast the 21 million cap is reached, but this can be ignored).

For the first time, an asset exists without any supply-side price constraint. To use the jargon, bitcoin is the first and only instance of perfect price-inelasticity of supply.

Market valuation with price-inelastic supply

We are all accustomed, unconsciously at least, to the behaviour of markets under normal conditions of price-elastic supply. Demand fluctuates, causing prices to increase or decrease initially, before supply of the asset adjusts to bring price into line. It is the persistent interaction of the forces of demand and supply which determines the price and its trajectory.

So what happens when demand is the only variable influence on price? For a consumption good, such as a foodstuff, this wouldn’t be that big a deal. Price would go up and down with demand, but demand would be based on peoples desire to consume the good - its “utility” to them - which is independent of price.

But for an asset that is used as a store of value, like gold or bitcoin, utility is not independent of price. The more an asset appreciates over time, the more useful and attractive it is as a store of value. That increases demand for the asset, whose price rises further, making it more attractive. This is the bubble logic of tulips and dotcoms and all speculative manias.

It’s worth noting that this can work both ways: the expectation of higher prices in future means greater demand now, which makes the price rise a self-fulfilling prophecy. But if at some point expectations were for lower prices, demand would fall and the prophecy would be fulfilled in the other direction.

In the short term you’d expect uncontrolled spirals in both directions, as control swapped between the alternate forces of greed and fear. But if you zoom out, one of these must win. It’s a question of pure human psychology - left to itself will people tend to drive the price of a pure speculative asset to zero or not?

This leads us to the two possible answers for the question of the ultimate fair value of bitcoin:

• $0, if downward speculation dominates in the long term

• $effectively infinity, if upward speculation dominates in the long term

Downward speculation cannot dominate

The $0 outcome seems fairly easy to rule out. For example, I promise hereby to buy any and all bitcoin at a price of $(1/21million) - thereby ensuring it will not reach zero while I’m alive and have $1.

(You could argue that if I owned all bitcoins it would be dead, and the market price would be $0. But it would only take one other diehard trading against me to produce a permanent nonzero price).

If downward speculative pressure stops at any price above zero it fails definitively - as the only force left will be upward.

In practice I’d think it is obvious to everyone that market forces alone are not going to drive the price of bitcoin to zero, and that upward speculation dominates.

Of course it could go to zero for other reasons - eg if some attack against it were to succeed, and it was effectively destroyed. This seems a more serious concern (and of course would itself be self-fulfilling if the market thought it likely). I may post separately about the incredible resistance of bitcoin to interference and attack, but here I’ll just say this possibility now seems very unlikely to me, especially now Wall St seems to be fully on board (here, here).

Its worth noting that bitcoin is unique in this property of durability. Other cryptocurrencies are not comparable in terms of their resistance to attack and government interference. That is why, to me, bitcoin can reasonably be described as the only asset ever to exist with price-inelastic supply - because that requires the asset to continue to exist..!

Where does net upward speculation take us?

If downward speculation cannot dominate, and take the price to zero, what then will be the effect of dominant upward speculation? What $ price level is too high?

Here it is important to remember: the price of bitcoin has no connection to any physical or economic reality. That means that the actual $ price of bitcoin is entirely arbitrary.

There is nothing special about any price level, be it $0.01 or $10bn. There is no number you can pick and say, for any reason based in reality, that it is too high. All that matters is the expectation of future prices and the resultant speculative pressure to move the price.

If the price level is arbitrary, then changes in the price level will not exhaust upward speculative pressure. In fact, as successive examples are made of the dominance of upward speculative pressure, one would expect its dominance to increase in ever tighter feedback.

This leads to the theorized event known in bitcoin circles as hyperbitcoinization, where a tipping point is passed and all other assets degrade in value against bitcoin at an accelerating rate. It is analogous to the compression of a collapsing star as the force of gravity it exerts on itself increases in a positive feedback loop until it becomes a black hole, or singularity, with infinite density.

OK but the price will not actually be infinity - it will be constrained by global liquidity

The absence of supply response means the price of bitcoin cannot be constrained to the kind of normal equilibrium seen in other goods. But that doesn’t mean no other constraints would ever be encountered - and indeed one will certainly intervene to stop unlimited eternal price appreciation.

To see this, consider the case of an OG bitcoiner. They may have taken the orange pill in 2012 and bought a few thousand bitcoin at $1. They agree with my arguments here, and believe the price in future will be significantly higher than its current level of ~$70k.

Under naive economic assumptions you’d expect them to continue to buy bitcoin - because everyone always wants more money, right?

This kind of unlimited profit seeking assumption holds pretty well at the level of whole economies - and ensures that all opportunities for making money will be taken by someone. But at an individual level it obviously breaks down. The OG bitcoiner will be very rich now, and might have 95% of their wealth in bitcoin already. They aren’t going to sell other assets to chase more wealth. In other words, they are already effectively “all-in”.

And this is the only constraint I can see. Dominant upward speculative forces will continue to push the price of bitcoin up, probably catastrophically, as everyone realizes that the price is driven purely by expectation, and that everyone else is expecting it to rise. Individuals will exit the mania only at the point when they consider themselves already “all-in”- that is, they are:

• aware of bitcoin’s properties and understand that it is a bubble with nothing to pop it, a one-way bet

• already so exposed in bitcoin that they decide to forgo further investment

The price will rise until everyone with assets is at this point. Everyone looks at their portfolio and says: “OK I think bitcoin is still going to pump but I’ve got enough now”.

What is the equilibrium price at the global liquidity limit?

We can now start to think analytically about this outcome. When will it be reached, and what will it look like? What would the price be?

For example, suppose people consider themselves to be “all in” when bitcoin is 50% of their financial worth. At this point they will stop buying more even though they believe they’d be likely to make money.

A quick search suggests the total global value of financial assets is around $250 tn. This just includes stocks, bonds and other financial instruments - and omits “real” assets, which could also be sold for bitcoin.

Say bitcoin just cannibalizes this $250tn in a zero-sum exchange - and the mania stops when the whole world has 50% of their assets in bitcoin. Everyone considers themselves “all in”. This implies a bitcoin price of about $6m - about 100x higher than we are now.

This has to be a gross under-estimate. For one thing, the 50% would only apply to the investor “at the margin” - that is, the last person to consider themselves all-in. At that point our OG would have a far higher proportion, and everyone in between would be >50%. There are also lots games likely to be played that ensure a much wilder ride up and a consequently higher equilibrium price. For example it would be rational for central banks to print money without limit, to buy as much bitcoin as possible - which could lead to far higher overall transfers of wealth, even though the marginal investor was still only at 50%.

Any further quantification effort seems a bit futile, but it’s worth noting that a simple description of the world this equilibrium produces is one in which, by definition most wealth is in bitcoin.

The end of upward price speculation should lead to stability

When everyone is “all in” the upward speculative pressure will dry up. This may cause the price to fall, but that would break the equilibrium condition - and we’d be back to where we started, with people sooner or later driving the price back up until they are back at their liquidity constraint.

Over time, this equilibrium should become apparent to everyone, and form a kind of “Schelling point” that everyone subconsciously coordinates around, leading to increasing stability - and marking the end of the era of active speculative bubbles. Bitcoin will have matured.

What will the world look like at bitcoin equlibrium?

There’s a lot more analysis that could (and I expect will) be done of this global liquidity equilibrium, but it feels like it is probably pointless at the moment. Long before it is reached, the world will have been completely transformed.

Here are a few of the more obvious changes we can expect in a world where most wealth resides in bitcoin:

• Bitcoin mining will dominate industry and power supply. Already bitcoin mining uses a non-insignificant fraction of global energy. As the price explodes under hyperbitcoinization, its energy usage will increase commensurately. Its not hard to imagine a situation in which >20% of the world’s economic activity and power use is in bitcoin mining - perhaps a lot more.

• Bitcoiners will rule the world. At a price of just $1m, Satoshi Nakamoto - if he’s alive - will be the world’s first trillionaire. As most wealth drains into bitcoin, economic and political power will no longer reside with the military-industrial complex, but it will be in the hands of OG bitcoiners. Who knows what the effect of this will be, but it has to be better than the constant warmongering and abuse of government power on which western society is currently based. Of course bitcoiners will also have incentives to do things to increase the price of bitcoin.

• Investment will drain out of productive capital. Many bitcoiners will hate me for saying this but even if you think (as I do) that bitcoin provides the hope of freedom for a world population whose alternative is digital enslavement - due to its property, which I haven’t discussed here, of enabling censorship resistant economic activity - its economic design means that it will provide significantly greater returns than other investments which society needs. Owners of capital will see they can make more money from bitcoin, and so will sell their factories and equipment. Only investments projecting higher returns than bitcoin will gain funding. Less capital employed reduces wages and overall welfare. It is possible that this problem would be solved by a new model of governance - based, necessarily, on bitcoin - but this is beyond my ability to foresee.

Before closing its worth noting: it’s not hard to see reasons to expect that bitcoin would be net bad for humanity - and possibly catastrophic. But even if we were all to agree that bitcoin should be stopped, it would be impossible for us to do anything about it. The game theoretic design of bitcoin is inescapable, it seems to me. Humanity cannot control bitcoin, it is something that is happening to us, and we will just have to go along for the ride.

Meanwhile, as satoshi said:

It might make sense just to get some in case it catches on.

Caution

This post is not investment advice.. If you do decide to buy bitcoin, know that:

• you don’t own it unless you hold your own private keys. Even owning a bitcoin ETF means you just have an IOU and are depending on the kindness of your counterparty not to keep it. I expect the temptation to keep it will become irresistible.

• there is no regulation or central control, by definition - and if you type “buy bitcoin” probably most results will be pure scams

• there’s no substitute for educating yourself. The information is all out there but you need to develop a good bullshit detector, and work out what information is trustworthy. This is a good place to start looking for resources. You can also try to meet knowledgeable and trustworthy people in real life who can help you, eg through bitcoin meetups.

Atsuki Tanaka and Takayuki Miyazawa, of Osaka Medical University and Kyoto University, wanted to trace the historical evolution of the omicron variant of SARS-CoV2 by studying viral sequences found "in the wild" and deposited in public databases.

In doing this they found around 100 separate omicron subvariants that could not conceivably have arisen through natural processes. The existence of these variants seems to provide definitive proof of large-scale lab creation and release of covid viruses.

Moreover the variants appear to form comprehensive panels of mutations typical of those used in "reverse genetics" experiments to systematically test the properties of different parts of viruses.

The authors also found exact matches to omicron variants in sequences originating from Puerto Rico which were deposited in databases in 2020 - over a year before the announcement of the discovery of omicron in South Africa.

Coupled with observations of implausibly low numbers of "silent" mutations in SARS-CoV2 variants, Tanaka and Miyazawa argue that all variants emerging since the original Wuhan outbreak are unnatural, and speculate that they represent an experimental program to test determinants of the infectivity and pathogenicity of SARS-CoV2 in the global population.

ADDENDUM: SARS-CoV2 may exist as a “viral quasispecies” - that is

“a population structure that consists of extremely large numbers of variant genomes, termed mutant spectra, mutant swarms or mutant clouds”.

This would make the appearance of reversion mutations less surprising. However it would not explain the lack of silent mutations in omicron and other variants (vs the original Wuhan variant), or the lack of silent mutations in the reversion mutants vs omicron, or the detection of omicron sequences in 2020 in Puerto Rico.

Thanks to for pointing this out - but it is still extremely difficult to see how these observations can be explained naturally.

Background: natural evolution proceeds by the accumulation of mutations

Before describing the study and its findings, it's worth quickly reviewing the basic principles of evolution of viruses (and all life forms). Feel free to skip this if you know it.

SARS-CoV2, like all viruses and organisms, is defined by its genetic information - which can be thought of as a string, or sequence of letters. In most organisms the string is made of DNA, but SARS-CoV2 and some other viruses use strings of RNA, a closely related molecule, to provide this information storage function.

The genetic material (DNA or RNA) is divided into “genes” - stretches of genetic sequence that each encode a protein. Proteins are active molecules which are synthesised by the cell, using the gene as a blueprint. Proteins are also sequences, but with very different building blocks. They don’t exist as simple strings that just store information, but instead form complex 3D structures which have biological activity.

When an organism reproduces itself the genetic sequence (DNA or RNA) is copied and passed on to the next generation. But the copying mechanism is error-prone, and occasionally a change, or "mutation" will be made. Successive generations will pass on this sequence, so mutations naturally accumulate over time.

The diagram below illustrates how this happens - with an original DNA sequence accumulating 4 successive mutations.

The effects of mutations on the organism determine whether they persist in nature

It's useful to consider that there are a few different general types of mutation, as judged by their effects on the organism:

• Many will have no effect. Some individual changes of a letter of DNA/RNA will not actually change the sequence of the protein encoded. Such "synonymous" mutations usually have no effect, so they simply accumulate over time in natural evolution. As we shall see, the lack of synonymous mutations is an important sign that the evolution of omicron and other variants is not natural.

• Of those that do have an effect, the vast majority will be deleterious - for the same reason that randomly changing part of any functioning system is likely to break it. Such mutations will disappear quickly from the population.

• Very rarely a mutation will cause a change with a beneficial effect. These mutations will then proliferate in future generations - as organisms carrying them will survive and reproduce more effectively.

So all life forms progressively accumulate mutations - some silent, and some beneficial. This is evolution.

The "unnatural evolution" of omicron

Let's now consider the specific case of the omicron variant of SARS-CoV2 and it's (presumed) evolution from the original Wuhan strain.

For this article we'll follow Tanaka and Miyazawa in focusing on just one section of the virus' string of genetic information - the gene encoding the notorious spike protein. They consider three officially-recognised variants of omicron - BA1, BA1.1 and BA2. For the moment we'll just look at BA1.

As with all evolution, changes in the spike protein occur through progressive accumulation of mutations in the genetic sequence that encodes it. In the case of omicron BA1 there are 37 non-synonymous mutations - that is, points where the sequence of the spike protein produced is different to that of the original Wuhan variant.

Tanaka and Miyazawa wanted to use public databases, where researchers from around the world deposit the viral sequences they have found, to trace the evolutionary history of the omicron BA1 spike protein - that is, to answer the question: in what order did these 37 mutations accumulate?

Tracing the order of accumulation of omicron mutations

There are two obvious ways to go about this - work forward or backward.

In the forward approach, you could look in the databases for versions of the sequence that have just one of the 37 omicron mutations, but which are otherwise identical to the original strain. This lone mutation must have been the first. You could then repeat the process to identify the second, third etc.

However variants carrying very early mutations would have been rare in the global population of SARS-CoV2, and may not appear in the databases.

A surer approach, and the one taken by Tanaka and Miyazawa, is to work backwards instead. That means starting by working out which of the 37 mutations is the last, or most recent.

To do this you need to find a sequence that includes all the mutations except one - and this must be the most recent mutation.

So Tanaka and Miyazawa made a series of 37 database queries using sequences each lacking just one of the omicron BA1 mutations - reasoning that one of the 37 should find a match, indicating the last mutation in the evolutionary progression to BA1.

It's interesting to imagine yourself in the position of these researchers, running queries for each of the 37 mutations, perhaps wondering which of them would turn out to be the most recent, and getting the answer.. ..ALL OF THEM*.

Well, all but 1 - which makes no material difference.

Their brains must have exploded.

A panel of variants with individually-reversed omicron BA1 mutations cannot arise naturally

In the figure below (Fig 2A from the paper), each row represents a variant of omicron BA1 found "in the wild".

The columns represent each of the omicron mutations. If the cell is colored, that means the variant carries the mutation. White cells show the mutation is missing, and the spike protein sequence is identical to the original Wuhan strain at that point.

If you think the table looks awfully neat, you’re right. It shows that, for all but one mutation in the omicron sub-variant BA1, a strain exists in which that mutation - alone - is absent.

In natural evolution by accumulated mutation, each variant only has one parent - because it was created by a single mutation event. So, taken at face value, these results imply that one of the variants is the parent of omicron BA1 (we cannot tell which), and all the others are children.

We can now answer Tanaka and Miyazawa’s original question and state the natural history of omicron BA1 evolution implied by these results:

1. The officially-recognized BA1 strain forms when the last of its 37 mutations occur (we don’t know which this is);

2. BA1 then undergoes 35 separate, parallel changes that each perfectly reverse one of those mutations to the sequence of the original Wuhan strain.

This is absurd. Perfect reversion of mutations like this, on such a scale, is completely implausible by any natural process.

The variants found by Tanaka and Miyazama can best be described as a "panel" of reversion mutations. This kind of panel is exactly what a researcher would create to systematically test the contribution of different elements of a virus to its activity.

Comprehensive reversion “panels” are also found for other official omicron variants

The researchers also looked at two further recognized omicron variants in wide circulation: BA1.1 and BA2. Remarkably they found the same "panels" of reversion mutations for both of them.

BA1.1 is very similar to BA1 - it only has one additional mutation, compared to the Wuhan strain, for a total of 38.

When Tanaka and Miyazawa made queries missing out each of these mutations individually they found 37 of the 38 existing "in the wild".

BA2 is fairly different to BA1 - they share 14 mutations with respect to the Wuhan strain, but BA2 only has 17 further (different) mutations for a total of 31.

When they looked for variants missing these individual mutations they found 29 of the 31 "in the wild".

"Recombination", or swapping of genetic material between different viruses cannot explain the Omicron variants either

The discussion above relates to evolution by progressive accumulation of mutations, in which each new variant is produced by mutation of a single parent.

There is another mechanism by which viruses and other life forms can evolve. "Recombination" involves swapping sections of genetic material between two different variants. Could the variants observed be formed by swapping genetic material between omicron BA1 and the original Wuhan virus?

Tanaka and Miyazawa go to some lengths to consider this possibility, but are easily able to exclude it.

For one thing, recombination would require omicron BA1 viruses and other ancestral viruses to be present in the same cell at the same time - because recombination can only occur in a cell, during the replication phase of the virus. This will be extremely rare given the frequencies involved, and the requirement to create so many reversion mutations - particularly given the timing of waves of the different variants, as discussed in the paper.

Explaining these reversions by recombination would mean a section of RNA in omicron BA1 containing the mutation to be reversed would have to be cleanly swapped, such that the mutations to either side were unaffected. There would have to be two "cross-overs" between the variants, one on each side of the mutation. But cross-overs require alignment of a stretch of common sequence between the two strains. For some mutations, the gap either side to the next mutation is simply not large enough to accommodate these cross-overs, and recombination is therefore impossible.

Recombination would also leave its marks in the flanking regions of the virus either side of the spike protein gene - and these were not found.

Omicron variants in samples from Puerto Rico - over a year before omicron's official detection

So Tanaka and Miyazawa were able to show that recombination could not explain the panel of reversion mutations they found. But in considering this possibility they stumbled on even more evidence that raises fundamental questions about omicron's history.

As they conducted database queries to look for signs that recombination had been involved, they found a matches to a sequence from Puerto Rico that was submitted in 2020. Further searches found 29 variants attributed to Puerto Rico that exactly match either omicron BA1 or BA2, based on spike protein sequences.

All these sequences were deposited in the database in 2020, over a year before detection of omicron in South Africa was announced in November 2021.

Lack of "synonymous" mutations strongly suggest artificial origins of SARS-CoV2 variants

As if all that weren't enough, Tanaka and Miyazawa point out another line of evidence that of itself is probably enough to conclude that omicron variants are unnatural.

The explanation of mutations above pointed out that in nature you expect to see:

• some that have some material and beneficial effect on the organism; and

• some that are "silent" or "synonymous" which do not affect the proteins produced from the RNA/DNA, and should not change the organism's ability to reproduce

These "synonymous" mutations which don't actually change the corresponding protein are, as you might expect, initially far more common than those which affect the protein itself. They usually would have no effect on the ability of the virus to survive, so they just accumulate naturally over time, alongside the more functionally meaningful acquisition of rarer beneficial non-synonymous mutations.

But the official omicron variants mentioned here all have just a single synonymous mutation in the gene encoding the spike protein - as compared to 31 to 38 non-synonymous mutations.

This makes no sense. Natural evolution would always be expected to create silent synonymous mutations at a greater rate than non-synonymous mutations that can only persist if, against high odds, they randomly result in a design improvement to the protein they encode.

The authors go on to point out that this implausible observation is not limited to omicron:

There were no synonymous mutations in the Alpha, Beta, Gamma, Delta, or Mu variants, [and] only one each in the Lambda and Omicron variants.

Omicron reversion panels appear to be part of a systematic experiment

The presence "in the wild" of almost complete panels of perfect individual reversions of virtually every mutation in 3 separate omicron lineages cannot plausibly be natural. Instead it looks exactly like a systematic exercise in "reverse genetics" to test the effects of each omicron mutation on the virus’ behaviour.

It's clear that some or all omicron variants were synthesised in a laboratory from which they were somehow released, as part of a deliberate program. Coupled with the lack of synonymous mutations in other variants, this suggests that all variants described after the original Wuhan strain have artificial origins.

The authors suggest the variants they have found are indeed part of an experiment to characterize the spike protein and the effects of mutations on the virus' behaviour:

Indeed, the lack of findings to date that many of the various mutations seen, especially in the early variants, are indeed associated with increased viral infection (van Dorp et al, 2020) supports the hypothesis that each variant was artificially synthesized to identify the amino acids of the S protein responsible for infectivity and pathogenicity.

Conclusion: this changes everything

If the observations and inferences in this paper are correct - and barring a pure hoax, involving fraudulent depositions to sequence databases, they certainly seem to be - then they provide indisputable evidence that the entire history of SARS-CoV2, at least subsequent to the emergence of the original strain, is artificial.

Someone, somewhere, really is doing all this deliberately.

Corrections

3 Sep 2023

• Some Most individual changes of a letter of DNA/RNA will not actually change the sequence of the protein encoded.

The majority of random single mutations will actually change the amino acid encoded. But the overwhelming majority of these will simply mess up the protein, so it’s still true to say that synonymous silent mutations should initially outnumber functional mutations.

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