On PCR Fidelity
The claim that PCR tests are plagued by false positives *must* provide other ways to explain why PCR positivity corresponds to future immunity.
This post will discuss my simple argument for why PCR tests are, on balance, accurate. For convenience, I will preface with a tangentially related response to JJ Couey’s response to my highlighting of Nick Hudson’s post, “The bioweapons bore.”
Couey’s response takes place at 6:15 to 17:10 of https://www.twitch.tv/videos/1727033554, hat tip to Cosmos Agent Roger 23 for notifying me of my cameo. I have sent an automated email via gigaohmbiological to hopefully schedule a call. My only goal with the following remarks is to illuminate myriad elements of context that, quite clearly, could not be fit into my character-limited comments in the cross-post from Wednesday.
Splitting the “Is GOF real” baby
(Readers can skip this and the next part. This one is just to establish provenance on questioning the GOF narrative.)
Viewers of Couey’s streams and readers of Unglossed alike would be forgiven for unfamiliarity with my previous work on critiquing the Gain of Function narrative, as this journal essentially has no particular focus in regards to SARS-CoV-2, the legal and political response to it, and the injections for the same. So, suggesting “GOF bad!” is a smokescreen for release is just one of a million subjects I have addressed.
Regarding the Project Veritas release of DARPA Ecohealth Alliance documents just over a year ago, I wrote:
Here, again, the spectre is raised that the DEFUSE proposal was designed from the start as a smoke-screen, and that the project never actually took place. The apparent (for now) need to retroactively plant the scare-words “Gain of Function” on the project certainly does nothing to purge the whole thing of the odor of a psy-op. It seems designed as fodder for “the opposition,” a lightning-rod to distract from The Big I-word. [Intentional release.] […]
Flash forward three years, and a concerted effort to pose the paper-trail for Daszak’s abortive DARPA-larping as evidence of a full-blown Gain of Function Manhattan Project crime scene plays out over the course of almost a year: All to distract from the readily-discoverable fact that Baric’s lab at UNC toys with SARS genomes as a hobby.
So, I am not new to pondering the implications of “infectious clones;” nor to the conclusion that the lab leak narrative was an op (as recently confirmed), i.e. that the opposition was being led astray by breadcrumbs leading to a fake monster.
But, I tend as a general stylistic habit not to use such terms of art, substituting my own “this-and-this-thing” terms to avoid misleading lay readers and to facilitate open thinking. I describe things as what they are; whereas terms of art describe things as how they work in the lab.
Thus, when the Bruttel, Washburne, VanDongen paper proposing to have discovered a restriction enzyme map was uploaded in late October, I used the term “DNA<>virus” platform. This was not done to somehow deflect credit from JJ Couey’s theory in advance of it even haven been uploaded. I remain reluctant to use the term “infectious clone,” because I don’t think it is a very good term, that’s all. It carries inappropriate connotations, such as that “real viruses” are distinct from the product of these platforms, which they are not.
Again, this was October 22; two weeks before the November 7 Rounding the Earth post that brought Couey’s new work to my attention.
Clone Wars
(Skip this part, too. It is merely a run-down of the events after October 22, to demonstrate provenance on my objection to the RNA virus genomic fidelity subject.)
In reply to that Rounding the Earth post, and to Couey’s video presentation, I commented:
Brian Mowrey Writes Unglossed Nov 7, 2022 · edited Nov 7, 2022
Will have to watch. All sounds pretty adjacent to my post today refining the implications of the BANAL-based counter-argument to the synthetic fingerprint paper, including a pretty map which places "GOF bad" squarely in the official counter-narrative factory bracket. *edit: which, I forgot to link
Brian Mowrey Writes Unglossed Nov 8, 2022 · edited Nov 8, 2022
Watching, it is incredible how on the same page you two are with me in this video [note that this was merely a real-time response to seeing someone else finally questioning the “GOF bad!” narrative]. Although I disagree with Couey that RNA instability is fatal to the pandemic narrative, I otherwise agree reality does not resemble a transmission only spread, sustaining the genome that is SARS-CoV-2 for this long implies a DNA master copy to re-release from. I'd especially point to my recap, a few weeks ago, of my argument that "vaccines causing variants" is an op to distract from intentional repeat releases (with updates to the "code")
"The synthetic origin paper shows what a farce it is to even care about the question [of vaccines causing escape pressure]. All the greek letter variants, from Alpha to the Omicron family (and a few suspicious sequences that never caught off the ground, from Central America and the US) should be considered lab-designed updates to the original DNA<>virus SARS-CoV-2 platform.
In May of this year, I strongly hinted that the entire information campaign to blame the vaccine for causing variants smells like an op; one that at first only applied to the vaccine-skeptic camp but since this summer has been expanded to the mainstream"
This was followed by an hour-ish zoom call with Mathew Crawford and JJ Couey. Unfortunately, the call was dominated with gossip about how so many substacks might be ops, or have handlers, etc. — so that I never got to bring up the objections noted in the comment. However, a follow-up call was tentatively agreed upon as a good idea (this never materialized). In view of the same, I regretted immediately not having had any chance to make clear that I have a very different argument for why multiple releases may be occurring; and particularly that I view the “RNA fidelity” aspect of Couey’s theory as weak. As Crawford was still my intermediary, I tried to forward these concerns:
The “discovery” notes in question had been composed before the call; as I wanted to bring up what I saw as problems with the theory; and, I knew that if we were to have another call intended for inclusion in Crawford’s show, it would be awkward to suddenly bring up my disagreements without warning (note that a full discussion of these topics is contained in the Should Variants Actually Happen? series):
Notes RE the swarm/defect thing, possibly illegible. Some of the highlights on the pdf are for unrelated topics:
limits of the swarm / defects theory
stabilizing selection in avian influenza / human M1 protein / swine/mouse (early PR8 passages) HA
[the example here was going to be early flu isolates. PR8 specifically was passaged from humans to ferrets to mice, and sustained via constant serial passage for years before advent of freezing circa 1940. This resulted in PR8 gaining tropism for mice (it is still the primary mouse-adapted strain used in experiments today) but not in antigenic remodeling - it was still the virus by which mid-30s exposure / infection to flu could be measured in neutralization tests. Likewise, swine flu when isolated in 1928/30 and serially passaged in swine for years continued to measure 1918-~23 flu exposure. The HA protein was totally stable no matter how many times it was passaged. More at link and more on stabilizing selection in avian influenza in the highlights of Webster’s Evolution and Ecology (pdf)]
[The attached version includes my highlights]
Co-infection of defects is still productive another flu lesson, gene packaging is random, some virions likely incomplete. Co-infection still results in productive expression (for example immune suppression). This would potentially be true in coronavirus as well. Since Orf1ab are the only ready-to-translate genes, incomplete RNAs can still contribute to immune suppression or formation of replication factories that amplify the expression of subgenomic RNA from other virions
What is even the point of offering a different theory?
All of this context (which hopefully you wisely skipped) is merely to show how it could seem like I am trying to sabotage or “distract” from “infectious clones.” But that isn’t the case. Instead, I had already been exploring the questions of multiple / repeat release in my own fashion for months. I think it is wonderful that Couey has generated a theory for repeat release that has captivated the “opposition.”
But should his theory be the only one?
In my view, no, as his approach to the question involves some intermediary premises that I don’t agree with at all:
Am I right? Is Couey right? It doesn’t matter (except the PCR point does matter, hence this post).
I just want the “babies” of intentional and multiple vector release to have more than one evidentiary basis. i.e., there is no reason to have only one argument for why vector delivery is occurring. Why should the eggs all be in one basket? What if not everyone is over-awed with the theory of RNA virus genetic instability?
Do I think vector release is occurring? It certainly explains some curiosities of the last three years, such as wild divergence in infection outcomes that are often geographically delineated; the fact that all existing clades of SARS-CoV-2 before BA.2 and BA.5 mysteriously died out, with VOC “reboots” from expired versions of the genome, and the alt-media and mainstream media campaign to blame the same VOCs on the Covid vaccines over and over and over again.
But, it isn’t consistent with sequencing data; especially in the BA.2 and BA.5 era. And my own attempt to prove a genetic signature for lab release in the 2020 VOCs was a flop.
If Couey sees this as an attack on “his” theory, the fact is that he does not own the theory of intentional and repeat release any more than I do. They are in the public domain.
Niche Argument
In this context, I realized on Wednesday that my second triangle was in fact a proxy for a more long-standing suspicion on my part related to the improbability of “novel” viruses crossing over from nature or from labs and being able to function and thrive in the human niche. One I had for whatever reason failed to articulate here or anywhere else before. Hudson did that, nearly perfectly, and hence my “endorsement” of his post:
This act alone can fairly be called an effort to “improve” my version of the argument for vector release vs. the original formulation. I apologize if doing so seems like any sort of attack on Couey. Again, I only aim to offer more than one argument for vector release, not to fight over who gets the baby.
The last two things worth noting are 1) The substack cross-post text field is character-limited, and my comments were 3 characters short of the limit. So there was no room to link to the SVAH series as a “for more about RNA virus genetic stability, with extensive citations, see my previous post” reference. Nor to insert “again, as stated before, my aim is to offer two arguments etc.” 2) I have no idea whether Hudson got ideas from Couey and then arrived to the argument in his post; I just found the argument convincing. I am not in the know as far as PANDA workplace tensions go.
Why PCR Is Accurate
The argument for PCR accuracy is simple.
By definition, a “false positive” PCR cannot tell you that an individual is unlikely to test positive again later. And yet it has been found in study after study that people who test positive are afterward dramatically unlikely to test positive again vs. the background rate.
Bear in mind, this is all in a context where if the deployment of PCR in general was a giant “scam” in order to prop up virus fear and get people more injections, it would be in the benefit of the scammers that previously positive people kept testing positive again. Because otherwise, that would suggest that previously positive people aren’t getting any more virus, i.e., they have natural immunity.
With that in mind, consider the older Cleveland Clinic study by Shrestha, N. et al. which made a splash in summer, 2021 for revealing that natural immunity is real (even as authorities were waging a propaganda campaign to denigrate the same, oops):
Let us replace “infected” with PCR positive, because that is all that was in fact measured:
Not one of the 1359 previously [PCR positive] subjects who remained unvaccinated had a [second PCR positive] over the duration of the study.
Nor did approximately 1,200 previously PCR positive, later Covid vaccinated workers. All told, against a background PCR positive rate of 4.3% over the study period, not a single repeat PCR positive was recorded (at the time of the preprint upload).
Precisely how would the purveyors of PCR nihilism purport to explain this phenomenon?
If false positives are such a big problem, why couldn’t Shrestha, et al., find any later positives in the previously positive people? What was protecting them from the “false” positives?
Is there such a thing as immunity to a false positive? What on literal Earth would such “false-positive-immunity” be based on? I honestly encourage readers to ask this of anyone who has ever hawked the notion that false positives are such a big problem.
What we have with the PCR nihilists, in other words, is a failure to allow theory to yield to evidence. In their theory, PCR should not or cannot work; but in reality, it literally, visibly, does work. Being PCR positive today means you are less likely to be it tomorrow; it tells you information.
Well, I choose to follow reality.
Is PCR positivity nonetheless merely proxy for “background coronaviruses”?
If so, just why exactly is it that in the final published results from Shrestha, et al., after the extensive genetic and antigenic remodeling ushered in by the Omicrons, this mysterious protection against PCR positives for SARS-CoV-2 goes away?
What about PCR tests that allegedly light up for the background coronavirus “swarm” could explain why previously-positive people, formerly virtually unable test positive again, suddenly now do so at the same rate as everyone else? Was the entire background coronavirus swarm swapped out?
Again, I honestly invite readers to ask purveyors of PCR nihilism this question. Why did Omicron increase “false” positives, in both the unvaccinated not previously “false” positive, and the unvaccinated previously “false” positive who for some reason before Omicron couldn’t “false” positive again? What explains that?
Obviously, nothing.
Whereas, once one accepts very simply that PCR tests are accurate for present infection, and thus future immunity, regardless of symptoms or anything else, nothing else needs to be explained at all.
The PCR test has multiplied SARS-CoV-2 genes because SARS-CoV-2 was currently replicating in the respiratory tract of the person who was swabbed; therefore this person is not likely to have PCR-test-detectable SARS-CoV-2 genes in their nose later on.
Isn’t that so much simpler?
What about the cultures?
At times, attempts have been made to substantiate PCR nihilism by pointing out that PCR positives can occur when viral culture positives fail. For example, someone might test positive on PCR on six different days, but only the 2nd through 4th of those days were accompanied by a positive viral culture of SARS-CoV-2.
This means, essentially, nothing. The three culture-negative PCR tests in this example are proxies for the three culture-positive tests. And all six of the six PCR positives is proxy for “an infection,” because otherwise how could any of the cultures have been positive; or how could any other studies show natural immunity regardless of cycle count?
While culture-negativity, and the cycle count thresholds that correspond for the same, might have implications for ability to transmit virus and therefore private and public policies regarding isolation, none of those is the same as showing that PCR positives are “false” for an infection having occurred. So this is simply a conflation of what “falsehood” is alleged to signify.
Further, we don’t actually know that a negative culture corresponds to an inability to transmit the virus to someone else. In all likelihood, the reality is a lot more complex (i.e. on this culture-positive day, doing the same actions, you could infect 10 people, on the next culture-negative day, just 1).
Base Rate Paradoxes
Of course, false PCR positives do happen. So, when should we be worried about them? Thanks to math, which is evil, the answer is “always rarely.”
A good example of such a paradox would be in the case of natural immunity. As established by Shrestha, et al. and myriad other studies, previously PCR positive individuals are unlikely to test positive again. This means, that if they are being tested, then any PCR positives that do occur are more likely to be false.
This could be a problem if you were asking questions like, “well, what about post-second-infection immunity?” because then you would be following a group of people who resembles what the PCR nihilists predict all PCR positive people should look like, i.e., not really protected from further positives.
It’s an obscure issue, applying only to contexts where there are no infections happening, such as between waves. Generally, nearly all PCR positives happen in waves, so this issue doesn’t “poison” the well as far as PCR tests.
Feel free to disagree with everything I have just said. But you won’t find anyone who can explain how a previously PCR positive person is protected from future positives.
If you derived value from this post, please drop a few coins in your fact-barista’s tip jar.
Calling PCR inaccurate is itself inaccurate to the point of falsity.
The issue with PCR lies in the cycle threshold that is used to delimit the test. For SARS-COV-2, PCR tests use a cycle threshold as high as 40.
However, no less than Anthony Fauci himself has said that Ct greater than 34 or 35 is only finding "dead nucleotides", and the CDC tells health agencies not to submit test samples for sequencing with Ct above 28 as those samples do not generally contain culturable virus. Last winter Rochelle Walensky also threw shade on PCR tests saying they tested positive on "fragments"
https://newsletter.allfactsmatter.us/p/did-rochelle-walensky-just-demolish
At high Ct values, PCR tests are not reliable for ACTIVE SARS-COV-2 infection. At Ct above 28, absent symptoms of active infection the test results quite possibly indicate prior and perhaps asymptomatic infection.
This is one reason why historical practice and WHO guidelines are for cases to be symptoms PLUS positive PCR tests (influenza testing is typically not even done unless one goes to the doctor with symptoms).
PCR testing works. That does not mean it is being used properly. There's considerable evidence to indicate it has not been for SARS-COV-2.
As someone who did COVID testing it was generally the idea that the tests were very sensitive. Depending on how samples were aliquoted it would be easy to get contamination, usually a random gene would amplify in another sample, or sometimes you'll get a "ring" of amplification suggesting maybe one well may have spilled over into neighboring cells.
In any case, there did appear to be a general idea higher Ct values ran into some issues. Usually at higher ends you may get one gene that amplifies at a lower Ct value, and yet the others may be over the cutoff, so you have to sometimes test again until you get more than 1.
My general belief with the Ct values is that they were derived from a hypothetical "infectious" value of virions. I believe this came from early samples and data from China. But if you assume X virions is enough to become infectious, then the Ct count may be set up with that infectious number in mind.
I think one of the problems with the PCR discussion is that people have a broad idea of what PCR is, but many people may not have spent time actually looking at how it works. I don't think many people know what primers are, or the different genes that can sometimes be amplified.
Everyone sort of knows that PCR amplifies, and the discussion is around whether the amplification is for too long via Ct counts or if the use of PCR would just be wrong.