About the guest: Kevin McKernan is the Chief Science Officer at Medicinal genomics and has been working the the biotechnology sector and conducting genomics research going back to his involvement in the Human Genome Project.
Episode summary: Nick and Kevin discuss: basics of DNA and RNA biology; mRNA vaccines and how they work compared to traditional vaccines; the mRNA vaccine manufacturing process; DNA contamination in the Pfizer and Modern mRNA vaccines for COVID; the SARS-CoV-2 spike protein; vaccine side effects; ivermectin and hydroxychloroquine; and more.
*This content is never meant to serve as medical advice.
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Episode transcript below.
Full AI-generated transcript below. Beware of typos & mistranslations!
Kevin McKernan 4:21
Was that Senator Ron Johnson humble hearing on all those COVID stuff. So you had myself Malone, Jessica Rose, Pierre quarry. long list of people who were just presenting evidence and all of the shenanigans going on in COVID. Yeah,
Nick Jikomes 4:42
we're gonna talk about a lot of that, I guess here. Why don't we just start off with some basic stuff. Want to don't you just tell everyone a little bit about yourself, your background, your expertise, and you know what you do at a high level?
Kevin McKernan 4:57
Okay, sure. Um, so My background started in, in this field in 1995. Actually on the Human Genome Project, I was started there as a member of the research and development team and shortly thereafter to the folks leading it left and left me in the reins, wholly unqualified, and I had to learn on the fly. So I started managing that research and development group to about a probably a 10 or 12 person group inside the Whitehead Institute Center for Genome Research was under Eric Lander and Lauren Lintons guidance. And we built basically the robotic platform and the DNA purification system to purify. We did about 20 million plasmids a year on that thing to do Sanger sequencing for the Human Genome Project. So, my role there was was related to the automation and the DNA purification chemistry and optimizing all the Sanger cycle sequencing stuff. And zash as that project came to a completion a lot a lot of companies were asking how to export that technology and and MIT held some patents on it. So we licensed those and spun them out to a company called Agincourt which became a really large DNA sequencing company. Actually, it was the largest commercial sequencing entity I think in the in the world. By probably 2004. Beckman came to acquire it in 2005. We had beyond just a DNA sequencing facility, it was a we had a bunch of DNA purification technology that was used to purify viruses and a variety of pathogens from blood. So they acquired that but in the process, there was a skunkworks project, we had to build a DNA sequencer that used us to sequence DNA off of single magnetic beads. And that was starting to show some promise, but of course, no one knew how to value it at the time, and so they decided to split it out into its own company called Agincourt personal genomics. And a year later, we presented data sequencing a coli genomes at Eygpt, which caught the attention of ABI and Illumina who proceeded to have a bidding war over the company. And Avi eventually won that bid and purchased Agincourt personal genomics and brought the solid sequencer to market. So I spent from 2006, to about 2011, working at EBI, getting this all sequencer to market. And we also at towards the end of that acquired Ion Torrent, which was another next generation sequencing system that worked on semiconductors. So I worked on that program, helping get that developed and out the door and then decided to split ways and worked on some other passions of mine, one of which was the cannabis genome I had been, I had a very large non compete, the company was now part of life tech, which is a bigger entity, which meant I couldn't really compete. My non compete man, I really couldn't work in that space. So I kind of just went off into the Ag space. And we started sequencing cannabis genomes, because we felt they were the genome had been sequenced at the time, and it had all these therapeutic compounds in there that could be helpful for cancer. And so we figured let's get the thing public and see if that helps kind of mature that field. That field got a little complicated. As you might imagine, growing a business in the cannabis field is difficult from a banking perspective, and the laws keep changing on you. So the company kind of pivoted back into doing clinical sequencing of people who might benefit from cannabinoids, so a lot of epilepsy patients mitochondrial disease patients, autism spectrum disorder. So we were doing exome sequencing on those cohorts as a clinical test. And that went on for about five or six years before we realize that cannabis market started to evolve and mature and we pivoted back into doing cannabis testing. So right now, my role of medicinal genomics is building PCR tests that target all the pathogens in cannabis that can either destroy it from a yield standpoint, or impact patient health, a variety of jurisdictions around the world demand ecoli, salmonella Aspergillus, a host of pathogens get tested for every every pound of cannabis that's sold. And we don't do the testing ourselves. We just make the picks and shovels that other labs used to do this type of testing. So we're mostly involved in assay development and genomic sequencing. Still to this day, we do a lot of genomic sequencing of cannabis genomes, and it's about 2000 of those public now on our website. And we've extended them to other medicinal organisms, philosophy comes to mind because it's has a similar, I'd say therapeutic profile for although it works in very different ways. It's one of these medicinal organisms that is, I'd say under studied in the current FDA regime, if you will, hard to get hard to get patents on these natural products. So a lot of people push them aside. And so we started sequencing. We've been through about 100 of those genomes that are up on our website. and publish some papers on that topic fairly recently. So yeah, I don't belong in sequencing vaccines can fish out of water, I suppose. But it, it came to us somewhat serendipitously. And I think because maybe your podcast and a few others highlighted some of our work in evaluating some of the early COVID tests, we were shocked that these COVID tests came to market without internal controls, because we could never get away with that, and in any other market. And so without those internal controls, it's really hard to gauge your viral load. And it seemed odd that we were racing these tests out the door without that, and perhaps there was a higher positivity rate early on in the pandemic. Many of the companies clean that up over time, but the kind of horses out of the barn at that point. And there's the so I wrote a paper on that, and one with Peter McCullough, which I think caught your attention in the last podcast, just talking about some of the differences between these vaccine mRNAs. And, and what was actually in the virus, which led to some discussions about frameshifting, which I think have recently been shown to be correct. There's a paper from Moroni that came out showing that the shooter yearning can cause some frameshifting, that is probably not the same type of frameshifting that you would see in the virus, because virus doesn't have those types of slippery bases. So
Nick Jikomes 11:22
yeah, I want to get to that, let's spend just a little time giving people who don't have the background, that you have some vocabulary, and just some, some, some basics, some basics that they can keep in mind, let's start super basic, but I don't want to spend too much time here. DNA versus RNA. So there's DNA and all of ourselves, there's RNA and all of ourselves. High level, what's the difference between DNA and RNA in terms of what they do, and what they're made out of?
Kevin McKernan 11:54
I think a good analogy is DNA is like what's on your hard drive on your computer in RNA is like what's in your task manager, like what programs are actively being run from your hard drive. So they're often fragmented and smaller in size, and they're ephemeral, they can go on and go off. So your DNA is this hard drive of all the programs your cell can run. And then the RNA whenever it wants to run a program, it has to turn that program into RNA for the cell to then turn it into proteins. So you have to think of it as all the program is possible that cell can run and not all cells are gonna run all programs at the same time. That's, in fact, what makes the cells very different is they selectively choose certain programs to run in order to be a heart cell versus a liver cell. So you get different programs being run in those two types of cell lines, which you can measure by sequencing the RNA. So the RNA will tell you what, what genes are actually turned on in a given cell? And how, how loud are they being turned on? Do we have one copy of the RNA? Do we have 100,000 copies of the RNA. And now the RNA is supposed to be fairly ephemeral. There's all types of circuitry in the cell to express it and then destroy it so that you don't have something that's constituency turned on all the time. But that process is quite delicate. And is the process that some of these vaccines are trying to hijack to get spike protein made? Yeah,
Nick Jikomes 13:13
okay, so So DNA turns into RNA. The RNA can be likened to the programs, your computer might be running at any given time, for a little while, for longer periods of time they shut down, they shut off. The RNA, the mRNA is made from the DNA, the mRNA can then be used to make proteins from it. In terms of the code here, we talk about the letters of the DNA and the RNA code. What are those letters and how they how do they differ between DNA and RNA? Well, ATC
Kevin McKernan 13:44
and g are the ones that are known to be in DNA. There are some exceptions, you sometimes have methylated versions of these bases, and you sometimes have uracil. But generally, uracil is mostly found in RNA. So when certain bases in the DNA get damaged, they might appear as a uracil. But there's a whole pathway meant to clean that up to get rid of these diamonds that have been turned into yourself. But RNA is always replacing that T with a u. So whenever you see RNA sequence, it would be a use eg there tends to be a U replacing the T. So that's one key difference in the language. You oftentimes find other modifications in RNA as well there's a very rare type of alteration to the use known as pseudo urethane, about point six to 1% of the of the use in any given RNA have a pseudo urethane in them, and the cell can further methylate that into n one methyl Suder urethane with a set of enzymes that methylate the superiority and so there's a pathway for about a very small infrequent percentage of the RNAs have these pseudo eurogenes which are, you know, we don't fully understand their role in biology to be on honest, when you do knockout mice, when you knock out the enzymes that that play in this cascade, really, really weird things happen. But it's I think it's important for folks to know that it's mostly relegated to Sno RNAs and T RNAs. It's very rarely found in messenger RNAs, these pseudo us, but they do exist in nature. And, you know, both of the mRNA platforms leverage the fact that that base was very rare and different, and replaced all of the use in their mRNA with this n one methyl pseudo you reasons of wanting to keep those RNAs around longer. The enzymes that we have that that turn these RNAs on and then destroy them are a little bit slower to act on the pseudo the N one methyl su urien, in the in the Pfizer Madrona vaccines, that was considered a feature not a bug at the rollout of this because their largest concern was injecting these RNAs and then having your cells destroy them before they could express by protein.
Nick Jikomes 15:58
So mRNA is Aug and see, most of our RNA most of the time, uses uracil as the EU, but there's a slightly different version that can be incorporated. And that happens naturally a small percentage of the time. And that affects probably, among other things, how long those mRNAs are lasting in the cell.
Kevin McKernan 16:19
Yes, there's some literature suggesting it may play a role in so their localization as well. The ones that are seem to have superiority on them tend to be more nuclear localized. But that's not that's not a hard and fast rule.
Nick Jikomes 16:34
And so in terms of the the mRNA, vaccines, the Pfizer and moderna vaccines that we're pretty much all familiar with at this point that have been used for COVID. At a high level, what was the intention behind these vaccines, how are they meant to work in contrast to traditional vaccines. So traditional
Kevin McKernan 16:50
vaccines would put a protein in your body and be injected into your arm and your body would build immune defenses against that that circulating protein and it made it's not meant to circulate just be in your arms, such that your immune system could see it and build antibodies. The approach here was instead of having to use a protein is was was to inject an RNA and have your cell make the protein for for them. Now that invites a lot more variation, if you will, or variability because not everyone translates RNA at the same speed, we don't know if they're all going to get that when the protein gets made if it's going to fold the same in every person, if it's going to get presented on the cell the same way. So you're several steps downstream in the manufacturing process, that you're sort of outsourcing to the patient and having their cells build these RNAs. Now, I think one key difference here is that when your cells are making these proteins, there's somewhat painting a target on their back for your T cells to come and destroy them. So in the case of a traditional vaccine, you're not decorating your cells with the antigen, to have your immune system attack your own cells, you're just teaching your immune system, how to defend against this antigen, but you're not, you're not really decorating your own cells with it. So I think one of the risks that we're seeing with these mRNA is is that when your cells in your own cells express these foreign proteins, they become targets for destruction. And that seems to be what may be happening. In myocarditis, we have this crossing paper out that shows there's mRNA and Spike protein in heart tissue, and there's a lot of inflammation in that heart tissue. And they can detect it 30 days later. So it may be the immune systems getting turned on against any cell in your body that's expressing these things. And you know that that could be if those are the wrong sets of cells, that can be very damaging. One of the other issues with these is that there's some biodistribution studies that show the SNPs aren't really contained to the arm, they can go all over the body. So you don't really know which which organ you're painting with these things. If you happen to this happens to get into your circulatory system, it could paint the epithelium of your circulatory system and then that epithelium gets destroyed, that could be causing clots. Mark tirado does some interesting work on this as bolus theory, I think has some has some legs to it, that you're stripping the epithelium of your circulatory system. And that's leading to all types of leakage, if you will, that can happen on the blood brain barrier could happen in your, in your aoto. aorta can happen in a lot of places that you don't want it to occur. So I think there's a difference a key differences. The protein is traditionally a proteins injected probably does a better job staying localized, it doesn't express is not made inside your cells, and thus painting targets on your own cells, thus leading to destruction of your own cells. I think those are two very key differences. And the third one is that by asking human cells to make the protein, we're now exposed to all the variability in the human genome, most of the population some people may make those proteins more effectively than others and there may be a much, much bigger, maybe a much wider variety in the expression levels of the actual antigen then just giving someone a really well known concentrated dose of a peptide. So
Nick Jikomes 20:05
So with a traditional vaccine, you're injecting a protein or a set of proteins from a pathogen directly into the body, you know exactly what the dose, how much of each of those proteins is in there. And it's just those literal proteins, you're not, you're not asking your own cells to produce that protein, the proteins are getting into the body directly. And then an immune response comes to that. And that trains our immune system, so that when we encounter the pathogen in the future, if we do, it's pre empting, that immune response, and that's how vaccines work. The mRNA vaccines are saying is we're injecting mRNA, instead of the protein, the mRNA is by design meant to go into our own cells, our own cells machinery, is then producing protein from that, in this case, that would be the SARS cov to spike protein, what you're saying is that now the protein is being made within and as you said, painting our own cells. And one of the other things you said is, there's probably going to be natural variability in how much protein you produce, or which proteins to produce, perhaps you're making a spike protein and some other variants just based on differences in the biology, from person to person in terms of the how quickly the translation is happening, how exactly that protein is folding and that type of thing.
Kevin McKernan 21:26
Yeah, and a few years ago, these were hypothetical concerns, because we're asking the cells to do the manufacturing for us. But the pharmaceutical companies didn't do a very good job proving that the cells made those proteins faithfully, they just showed we have antibody response, which there's we now know there's, there's there is high variability in this due to this base that they put in. So they put in this in one metal suit or urethane so that it would evade the immune system and then last longer. But that came with some compromise, which is that the ribosomes that read RNAs that have that many modifications, get confused, and they sometimes slip and get out of frame. And make, I think, I think the Moroni paper said 8% of the proteins were frame shifted. So we're already taking an 8%, loss and fidelity, making unknown proteins to get the spike manufactured by ourselves, that wouldn't be the case, if you injected a purified protein, you'd be able to make it outside of the body, purify it, quantify it, to put in only what you're looking for. But when you start asking for your cells to perform his manufacturing for you, and you have to, you know, put some camouflage on the RNA to sneak it through the immune system, you're inviting some some fidelity issues with the translation process that has now been exposed through the Morrone paper. And
Nick Jikomes 22:45
so just to tie some of this stuff together for people mRNAs naturally, are, as you said, they're ephemeral molecules, they're not supposed to last very long in the body, they're supposed to be produced for set periods of time, you don't want them sticking around too long. So our bodies have lots of enzymes to quickly break them down. It sounds like what you're saying in terms of the mRNA vaccines that were manufactured for COVID. They use this pseudo Euro Dean in place of the Euro cell, so they use that slightly different version of the EU in the RNA code. And that's because my understanding is if you use the normal you that the mRNA is not going to last really long enough, it's gonna get broken down right away, and you won't actually generate an immune response. So it has to do with increasing the stability of the mRNA. So that actually sticks around a little bit longer. Yeah,
Kevin McKernan 23:29
so there's a whole class of rnases that localize in different cell compartments and tissues, but the one that Carrico was was really concerned about was something known as RNase L. And they demonstrated that RNase l was less active on mRNA that had this modification to it. So they thought this is a great way to get the RNA to last longer, and they were right about that it does last longer. But I think the maybe the concern that the models didn't predict is that clearly in some patients, it's lasting a lot longer than even a forecast, they were suggesting 48 hours, we've now had papers out showing it 28 days in plasma 30 days in the heart five days in breast milk, 10 days and placenta. So they're picking up this mRNA you know, anywhere between five to 30 days later and various tissues that have been surveyed. The spike protein itself is sticking around longer. And there's one paper out showing 187 days where they're picking up spike protein. So I don't know if that's the RNA is still around and we're not detecting it and it's still expressing or if the Swype proteins really hard to degrade. I think there's still a lot of questions to be answered as to what's the mechanism of action of that of that persistence. But it's possible that these LPs are getting to stem cells which are immune immune privilege, so immune system won't attack your stem cells. And if you happen to get an LMP into a stem cell, well then it's you kind of have it camouflage inside your body and it could be expressing spike protein for much longer than
Nick Jikomes 25:02
what is an L L MP?
Kevin McKernan 25:05
Oh sorry, lipid nanoparticles are the, it's kind of the fat bubble they put these RNAs into so they can get into your cells. That means it's protected from a lot of the lot of the nucleases that might degraded outside of the cell. And it kind of Trojan horses its way right into a cell. Okay, so
Nick Jikomes 25:21
a lot of a lot of the design of these vaccines was aimed at making sure that the mRNA actually got into the body and lasted long enough to do what we wanted it to do. Yes,
Kevin McKernan 25:33
yeah, that's, that's key. And I don't know how much attention was put into understanding the clearance of it. You know, how having something lasts for for a long time may not be a desired outcome, you may, most immune responses are finding a small antigen, and preparing the body to amplify its response to that the second time it sees it. So you don't necessarily need a lot of antigen to deliver, to get to build a response, I think they were in such a new space here. Their concern was, let's make sure we at least get a response. So let's make the mRNAs last long, without as much concern over what happens if they last too long. And this persistence, create disease, it maybe wouldn't create disease, if it wasn't expressing a protein as notorious as spike protein, maybe it's maybe the platform is fine if it had some other type of, you know, benign protein in there. But the combination that we that there's a protein that now has a lot of publications on its toxicity, and persistence is one concern. Now there's, there's there's other concerns out there that well, what if you just had naked LLPs? With nothing in them? What damage? Would that do? We don't have an answer to that. It could be that just these NNPS, bombarding the cells with any foreign peptide turns the immune system against them, and you're really just inviting the immune system to erase a certain percentage of the cells. I mean, there's, there's some, you know, numbers on how many LPs are in this, I've seen literature that it's anywhere between like 50 billion to a trillion, I tend to think the 50 billion numbers more accurate based on just surface area volume calculations I've done but that's still, you know, 50 billion, you probably have, you know, 40 trillion cells. So you're talking about one and 1000 cells getting painted for destruction, which wrong cells, that can be a problem.
Nick Jikomes 27:22
So when we talk about the the mRNA, vaccines for COVID, they contain the mRNA, which encodes the spike protein, but it's not the it's not identical to the native mRNA that's in the virus, it's using this modified you in the code. And they're also encapsulated in these lipid nanoparticles. So it's not just like, we took the straight mRNA chunk of mRNA. From the virus that encodes the spike protein, we took that we modified and tweaked it, we wrapped it in these protective lipid nanoparticles. And that's what goes into the body.
Kevin McKernan 27:57
Yeah. And that actually is an important point, because as I'm sure we'll get into, if you start having contaminants that are in these LPs, they're you some of your defense mechanisms to get rid of them can't do their job. So when you wrap this in a fat bubble like that, it protects it from a lot of the nucleases in the blood. That's true for the RNA and any potential contaminating DNA that's in the shots. Typically, if you inject DNA into somebody that has like a 10 minute Half Life in the blood, it's not a big deal. They have a lot of previous vaccines that have had DNA contamination in them when they're injecting those peptides. But that stuff is gets destroyed pretty quickly. The moment you package it into the LNP. You're bypassing that whole defense mechanism when you're delivering that DNA and then RNA straight to a cell. So now it's there's an unknown as to whether you know what the tolerability is how much DNA can we tolerate under those circumstances that hasn't really been addressed by the FDA?
Nick Jikomes 28:54
In basic terms, can you walk us through just the basic process by which Pfizer and moderna manufacture the mRNA vaccines? How do they go from raw materials to the final product? Well, it
Kevin McKernan 29:07
starts with your initial question. So they start with DNA. And they take an RNA polymerase to express RNA off of that DNA. And so they use that DNA almost like a, let's only call it a template, but it's almost like a printing press, you have a system that you can just print RNA off of. Now, there's two different ways you can generate that DNA. And you know, Maderna, from the beginning, had a plasmid that was making your RNA. So trial went on with the plasmid there, they took a different day they took their their their clinical trial reflected their mass production. Pfizer made it made a bit of a switch here, they started not having enough DNA, so they PCR amplified the region of DNA that they wanted the RNA to make out of a plasmid. So usually what a plasmid is is a circular piece of DNA that allows that DNA to replicate in stores very well, because it's circular, you can put them in bacteria and bacteria can harbor these plasmids. And you just grow the bacteria out. And it creates about 100 of these plasmids per cell. And the coli cells double every 30 minutes if you give them the right temperature and nutrients. So it's a great system has been used for ages in the biotech system to replicate DNA inside of another organism. So Pfizer ran their clinical trial amplifying PCR amplifying off that plasmid DNA. And then they made RNA from the PCR product. Now, the reason that's materially different is that when you amplify a plasmid like that, you can then your your amplified material was about a million times higher in concentration than your background, you could put a very, very small amount of plasmid in amplify it and get a million fold amplification, and about 20 cycles, PCR. And that means that your contamination is a million fold diluted. So then you can then take that very clean DNA and make RNA from it. And then when you're done making that RNA, you now have a pot that has DNA, some DNA template and lots of RNA that you just made. And conventionally, they would like to erase that DNA and they use some enzymes like nucleases to get rid of that DNA. And that is something that seems to be failing in their process, there seems to be a failure to get universal DNA since the enzyme they use so to completely eradicate this DNA. So in the process of scaling this up, they they went, they did the trial on this PCR generated material, which is very clean. And then when they had to scale up, they switch the process to process two, which didn't which skip that amplification step and they tried to get the plasmid DNA directly into the into the RNA generation process. And since they skip that step, what that means is the complexity of the background DNA is now the entire plasmid, not just the region, you amplify. So this means another like 4000 bases of DNA come through, that have an antibiotic resistance gene that have an SB 40 promoter that have to they have a variety of other components in the backbone of this plasmid. So there's more background genetic material that comes through when you do this, you skip that PCR step. Now they were supposed to do as a study comparing process one to process two across children 52 people, and they threw the towel in saying it's not gonna matter. It's not big enough of a study to really find anything. And the EMA looks like they let them off the hook on that. So we don't really know if there is a different adverse response rate that would be witnessed and Process Two versus process one. That's been something that Richard Levy And Josh blitzscale have brought up in the BMJ showing that this is, this is unusual in the biotech space when you it was compact, complex biologicals, like this, the actual process is the product, because there are so many different components in living systems like this, that when you're when you're using a coli to amplify your DNA, you can have a host of different contaminants that you can't necessarily measure that can come through the process. So whenever there's a process change, they consider that to be a new product, because you can't fully characterize everything that might be in that background. Now, one, one background in particular, a lot of people highlight is when you're working with plasmid DNA, and you don't amplify it, you have to crack open those E. coli cells and get your DNA out of those cells before you make RNA from it. And that process can be prone to leaving a lot of coli guts in the equation. By guts. Most people are concerned about endotoxin that comes through on the coat of the E. coli cells crack open those cells. And now endotoxin, which is known to be really aggressive immune stimulator comes through with the plasmid DNA. That can be very tricky to measure just nature that compound, but that's something that is if it is there. We don't know how much of it's there, because most of the documents we're finding have the endotoxin levels redacted. But if it's there, that is known to create anaphylaxis, anaphylactic shock. So that is something that could be responsible for some of the acute reactions that people see. I don't think the DNA contamination is creating any of these people fainting or anything that cute, it's something that might be more long term of a concern.
Nick Jikomes 34:20
So so when we think about so someone goes in and get gets their vaccine, the mRNA vaccine, you know, they want to talk about what's in that syringe. So there's the stuff that's supposed to be in there by design. And then there's the potential that other things that we don't want to be in there that aren't supposed to be in there are also in there. Starting with the first group, the stuff that's in there by design, you've got obviously the mRNA, which has this modified you in the code that we discussed. You've got the lipid nanoparticles, the little fat bubbles that are like little Protective Shells around the mRNA give us a sense in a single dose of say the Pfizer vaccine, how many mRNA molecules are in there? How fool is it with these lipid nanoparticles and what else is in there by design?
Kevin McKernan 35:04
So there shouldn't be about 13,000,000,000,013 to 14 trillion mRNAs and Pfizer dos Maderna has got three times that amount, the closer to 42 trillion mRNAs. And those are we estimate are probably in, you know, 40 to 50 billion lipid nanoparticles. So do the math on that it's couple 100,000 of these mRNAs per for LNP. There's some cholesterol and peg and other ingredients that help stabilize these LPs. But I think those are the two key things is that that mRNA is there and the lipid nanoparticles there, what we discovered is that there's also DNA inside those LPs. And that's broken up, it's fragmented, but it's at there's billions of copies of those as well, not trillions, but billions.
Nick Jikomes 35:51
So so you've got billions with a B of lipid nanoparticles in say, a Pfizer vaccine dose, each one of those is going to contain on the order of hundreds of mRNA molecules. So you got billions of little fat bubbles, trillions. It sounds like of mRNA molecules. How did you guys go about looking for DNA contaminants that were in there? What was that process? How did it
Kevin McKernan 36:15
Yeah, so when we were we were actually studying hop latent viral infections in cannabis, this is something that's devastating the cannabis field. And we're doing just boatloads of RNA sequencing of plants that were infected at different points in the infection cycle. And when you do RNA sequencing, as we mentioned before, you should get sequencing that lines up only over the genes. But if you get sequences that aren't in the genes, there's probably something wrong with your RNA sequencing system. And one, one week we came in, and that's what happened, we saw sequencing that was all over the genome, and we're like, okay, something's broken, we're not capturing mRNA, we must be capturing genomic DNA or, or we're somewhere there's a problem, we shouldn't be getting sequencing all over the genome like this. So to solve that problem you typically do is you spike in a known mRNA as a control. If you can't capture that, then you can pinpoint, okay, the magnetic beads that pull down the RNA are broken, or maybe the DNA step is broken. So I needed an mRNA that had that was pharmaceutical grade had a poly a tail and said of ordering one, I was like, Well, I've got one of these on the shelf, someone shipped me, that's a Pfizer vaccine, that should be that should be pharmaceutically pure, let's pop that thing in there. And if that doesn't come through our RNA sequencing pipeline, then we can figure out what's broken about it. It did come through the sequencing process, we did identify, we had a bad DNA base enzyme that wasn't chewing up the background DNA, which is why we're getting sequencing everywhere. But in the process, it also revealed that there was the Pfizer's vaccine plasmid was still in the vials. So we ended up with the
Nick Jikomes 37:48
piece of circular DNA that they use to amplify to get the mRNA pieces
Kevin McKernan 37:54
that was still in there, that was still in there billions of copies of it per vial, or per dose, I should say. So that was a bit shocking, because we were expecting to find any of that we got you know, we got these assemblies back that had spike protein in there. And we're like, well, Spike should be 4200 bases. Why the heck is this thing 7800 bases long, and we threw it into snap gene. And that's when we saw Oh, there's an SP 40 promoter. There's a kanamycin gene that this is the expression vector you
Nick Jikomes 38:19
saw, you saw the you saw the carcass of the DNA plasmid and the things that we know are in it. Yeah,
Kevin McKernan 38:25
there's obviously a blueprint of how to make it basically.
Speaker 1 38:29
Oops, not so how, how many
Nick Jikomes 38:33
of these experiments did you do? How fresh was that vaccine batch that you had is how confident are you basically that? Oh, yeah,
Kevin McKernan 38:39
so that's a good, that's a great point. That's something that people always bring up. So they weren't very fresh, actually, people shipped these to us. And I ignored the request to sequence them for probably six months, chucked them in the freezer and forgot about them. And then when I had an emergency, I was like, Ooh, that that thing will work. And by the time I pulled this stuff out and used it, it was in fact, an expired vial. Now people have since gone back and replicated this with non expired vials. Philip buckholts Did some of this work. David speaker did this work in Canada as well.
Nick Jikomes 39:05
So other people independently made this observation using different fresh batches,
Kevin McKernan 39:09
which has been very helpful because people had good reason to throw tomatoes at us, if you will, when we published this. They were mad that we had an expired vial that we that we sequenced, but you know, these, there's no reason to believe it. And the expiration date would actually destroy the DNA or make more DNA in there.
Nick Jikomes 39:27
Right, right. Yes. 20. You wouldn't expect an old batch to have a DNA contaminant that wasn't in a fresh patch. Right,
Kevin McKernan 39:33
right. Unless someone some Gremlin got on there and put it in there. But the fact that it was Pfizer's expression vector was a pretty good fingerprint that Pfizer put it in there and had their spike sequence in it, and it had what looked like a about expression vector. And the other thing to know is that the expiration dates weren't some hard science, they often would just change them announced that oh, this expired vial can now be used. So expired viruses were injected into people that didn't stop them from using them. In the field, it just was something that was a critique of the, you know, the way we went about sequencing this. And that's just because we didn't, we didn't set out to sequence this as any type of grand experimental plan, it was kind of an accident. And so as we did to try and help there as we built PCR assays to make it really easy for other people to replicate this in other places, and so they wouldn't have to go through this expensive sequencing process, and that, that indeed, helped the replication of the work in other places. So
Nick Jikomes 40:30
the implication here is that in the mRNA, vaccines that were actually used, you had not only the mRNA, and the lipid nanoparticles, all the stuff there by design, but you also had remnants of the DNA from the plasmids used in the manufacturing process of these vaccines. I guess the next question is, how big of a concern is that? Is it? Is it plausible that those are going to cause an issue in a human being? Or are these DNA sequences likely to be pretty inert and not really doing much of concern?
Kevin McKernan 41:05
So I think that's where a lot of the debate lies is what's the clinical implications of this? I don't think anyone's doubting their existence anymore. Now that there's been so much replication. We've had the EMA the FDA, and Health Canada come out and admit that okay, yeah, this, this could be in there. They trust the manufacturer who's measuring this to say it's below some certain limit. I mean, Philip buckholts, brought up a very good point on this, which is your limits were set based on the decay rate of natural DNA being injected in traditional vaccines, this is a different beast, we have them in LMP. So they're not going to decay. And the transfection efficiencies of this DNA is going to be very high. So the prior regulations on this around 10 nanograms of DNA per dose, now those those guidelines have changed 1000 fold over the last couple of decades since the end, after in the Reagan era, they put in the nCVA Act, which is the National Cancer National Vaccine Injury act. And that gave pharmaceutical companies a bit of liability shield on vaccines. So since then, the regulations have moved from 10 pico grams up to 10 nanograms with traditional vaccines that don't have LPs. So we're in a different world now, where we have LPS that are facilitating the CNAs entering so And arguably, that limit should be revisited. There's another thing that I think we've learned in this process, which is that maybe those regulations shouldn't be just about any DNA, what if the DNA is a plasmid that can replicate? You know, now, now, you can slip something in that through that loophole, and get the DNA to make more of itself once it gets in the cell. So if we have the capacity today to sequence every piece of DNA, and it's in there, we didn't have that back in 1984, when they were conceiving of these liability waivers. But today, the cost of sequencing has gone down 100,000 fold in the last decade. So there's no reason why we can't know precisely what type of DNA is in every single contamination event. So a lot of things have changed since those roll those those rules were written, and they probably need some some revision. So alright, let's get to the clinical implications. What could happen this DNA, if it gets in, I'm a little bit less concerned with Maderna is only because the plasmid the nature of the plasmid they have contaminating has, it doesn't have a few of the features that are in Pfizer, and they have they seem to have a better job. They're lower in DNA contamination levels than Pfizer. So if you get if you get through the patent literature, you'll you might understand why that that Maderna is actually has a patent out there, that speaks to the residual DNA risks, and they invented technologies to get rid of it. And it looks as if those technologies work because they have less of it. But inside that patent from Maderna, it'll point out that this DNA is a risk of insertional mutagenesis, which means it can insert into your genome and cause can cause cancer. It's a hypothetical risk if they didn't present data showing it's causing cancer and people that just knowing molecular biology, if you put DNA into a cell, and it can get to the nucleus, it can integrate into your into your, your genome through a process known as either Hamilton non homologous end joining or micro homology mediated and joining us, it sounds
Nick Jikomes 44:13
like anyone engaged in this type of molecular manufacturing process. It's, it's a known thing that you are probably gonna get some amount of DNA contamination in here. It's known to the extent that Maderna actually invented methods to reduce the levels of contamination from that residual DNA. So they had less of it, it appears in the Pfizer vaccine. But the other the other complicating thing here is, you know, even with other injectables that are known or could have DNA contaminants, some of those thresholds you mentioned around what we allow, are, are based on the idea that if it's naked nucleic acid in there, it's going to degrade pretty quickly at some known rate or some rate that we can estimate but because we're using these lipid nanoparticles to shield the nucleic acids with these new vaccines. If you have DNA contaminants in there, they themselves might be protected, protected by the lipid nanoparticles which might, which could hypothetically enable them to stick around long enough to do something where they would simply be degraded if they weren't shielded. Yes,
Kevin McKernan 45:20
yeah, and we've done some work. To move this from hypothesis to a little bit more sound theory. One thing you can do with these vaccines to estimate how much DNA is in the lipid nanoparticles or outside of lipid nanoparticles is you can take them and treat them with the enzymes that Pfizer is using to try and get rid of this stuff known as DNase. One. And it's an enzyme that destroys DNA, if you treat their vaccines with DNA is one you won't see a CT shift and PCR for the vaccine DNA, which tells you that most of this DNA is actually protected from the nucleus, probably inside the inside the LPS. The other thing that we've done very recently with Uli Commonwealth in Germany is she's taken these vaccines and treated ovarian cancer cell lines with them, and then grown them in flasks, and then passage them into several rounds of growth, to show that the DNA persists inside the cells through several passages, so that tells you as well, that the DNA is in the cells. Now, for those not familiar with cell passaging, you treat these cells with the vaccines, a small amount of them a third of a dose, I think was what she used in her case. And then you see those cells into a dish and let them replicate a couple times to go to Confluence, then you rinse all the stuff off the cells to clean off any the residual vaccine, take a portion of those, PCR what's in the supernait and PCR the cells and then put the new cells into another flask, let them grow out again, rinse them off, and then PCR the supernatant in the cells. When we do that we can track how much RNA is outside the cells and how much is inside the cells. And we can see this DNA inside the cells through several passages. That tells us that the LPs are in fact delivering this DNA into the cells going through cancer cell lines. They're not they're not patients, because it's more complicated to this work on patients. So
Nick Jikomes 47:09
yeah, so let's let's really break this down for people. So you've got human cancer cell lines growing in a petri dish, you put the mRNA vaccine, you dose them with mRNA vaccine, you just spray it on to the cells, you let them divide some number of times, and then you're saying you can find the residual DNA contaminant from within the vaccine inside of the cells. Yes. And is that are they inside the cells in a lipid nanoparticle? Are they integrating into the genome inside the cells? That's a good question. I
Kevin McKernan 47:39
don't think our experiments really address that. So we were doing PCR of the supernatant and of the cells, and we could see the PCR signals in the supernatant in the cells in passage one and passage two, and that told us that there's a good portion of this DNA that's actually in the cells. The other thing she did is she stain the cells with immunohistochemistry for spike, to see like, okay, it's in the cell are they expressing, and she and she got the cells to be about 50% SPIKE IHC positive, which is what she's aiming for, it's not to have every cell transfected, but maybe half of them transfected. So those are the those are the two bits of information we have, we then went and did whole genome sequencing on those cells. And that revealed some other interesting information. The whole genome sequencing gave us about 3,000x coverage over the vaccine. So in sequencing coverage is the number of times you sequence the molecules. So we at any given base in the vaccine, we had at least 3000 reads covering the vaccine. And in the actual ovarian cancer genome, which is a much bigger genome, we only have about 3030 fold redundancy and sequencing. So there's about 100 to one ratio of plasmid to to the actual ovarian cancer cell line. That's perhaps not too surprising when you think about how big the human genome is, and how small this plasmid is. And when you deploy this much sequencing, you should expect to see more of the of the actual vaccine there than the human genome, at least from it. From a coverage standpoint, these are only 7000 letters long the human genome is 3 billion bases long. But I think what was most shocking to us is that we could see that there were variants in the vaccine plasmid backbone that didn't exist in the vaccine that we sequence that was outside of the cell. So as a control, we sequenced the vaccine directly. And then we sequenced the cells that were treated with the vaccine. And when you look at the assemblies of the vaccine, in the cells versus outside of the cells, they're different. There's a fair number of variants that are only in the origins of replication in the plasmid that tells us this, those are doing something with that DNA, perhaps replicating it.
Nick Jikomes 49:47
Because the plasmid DNA remnants that were in the vaccine, get into the cells and persist for some number of cell cycle divisions and replications And because this you found variants. So the the sequence inside of the cells sometimes did not match the original sequence that you found in the vaccine itself, that implies that perhaps the DNA, this contaminated DNA is being replicated in the cells. And as a natural consequence of being replicated some number of times there's going to be some amount of mutation.
Kevin McKernan 50:20
Yes, and and all those mutations were concentrated in three regions in the plasmid that are known as origins of replication. There's an f1 origin of replication, there's an SP 40, origin of replication, and there's a bacterial origin of replication, we saw the only variants we saw were in those regions, which leads us to believe if you look at the sequence depth of coverage, there's a little bit of a pull up in those regions suggesting some of those things might be getting replicated by the DNA polymerases inside the cell. That's probably the most interesting evidence we have in terms of its bioactive, like the DNA is the only way that that that DNA gets changed as if it's if it's in contact with the cell, that's, that's changing it. Or as the control of vaccine didn't change at all that that's, that's another hint we have that this is inside the cells because you won't get these variants, if you just leave the vaccine out in, in sequence that alone. So there's a couple pieces of evidence pointing to the fact that this DNA is getting into the cells and it's bioactive. And and now there's there's another bit of evidence that we have here that needs further replication, because when you start talking about DNA integration, you have to be very scrupulous on on ruling out all types of artifacts that can happen when you try to measure this. So we did find two regions where there was spike sequence joined to human sequence, one on chromosome 12, and one on chromosome nine in this dataset. Now, the one on chromosome nine, another researcher in Japan, Dr. Hiroshi Arakawa has kind of sleuth that out and thinks that might actually be an artifact of our the process we have. But the one on chromosome 12, he believes is real, and has presented some additional evidence that there is evidence for micro homology mediated enjoining. There, there's a short set of sequence in spike that's similar to chromosome 12, that has fused with cumulus chromosome 12. Now, we have only two reads that are covering this out of the 30x coverage we have. So it's it's not present everywhere, which is expected you're not expected every cell to get to get integrated at the same place. But we've got two independent molecules of Illumina sequencing that have about you know, 60 bases and neither side that prove this is in fact a fusion between chromosome 12 and spike. Now, we don't know if this fusion is occurring in the nucleolus. Or if this is some type of extra extra chromosomal DNA artifact in cancer cell lines, there's this process known as Cromo. thrips, is where the, since the DNA repair enzymes are somewhat dysregulated, you get shattering of the chromosomes. And so there's a lot more extra chromosomal DNA and cancer cells. And we could have picked up in integration event to the extra chromosomal material, which isn't necessarily as persistent as something that would be an integration event in the chromosome. The reason we're presenting that caveat is that we only have one junction of the integration event covered with these with his evidence, usually, when you have an integration event into genome, you should have chromosome 12 on one side, and you should have chromosome 12. On the other side, and spike in the middle, we've covered a spike human integration event on one end, and we didn't see it on we don't see the other end of it. So either we didn't have enough sequencing depth to find it, or it's an extra chromosomal debris that we've picked up. But that's another strong evidence, the DNA, the only way that DNA can fuse to human DNA is if it's inside the cell. So it's clear to us that DNA is getting transfected into cell lines. But the jury's still out on whether this integration event is something that's heritable, it could be something that occurred in cancer cell lines only, and it's gonna get thrown out in cell division. And we need more depth of coverage and a lot more sequencing to confirm that it's actually a chromosomal integration event.
Nick Jikomes 54:08
So, you know, these are these are experiments, their cells growing in a petri dish, their cancer cell lines, they're not healthy human cells. We're not talking about what's happening in human beings. But of course, that's what's going to be in the back of everyone's mind is, to what extent is it plausible that this type of thing can actually happen in a human being who received these vaccines? How do we begin to think about that? And what does the process look like for actually determining,
Kevin McKernan 54:33
I think, a good This, of course, requires some skill sets we don't have. So we usually need to get an IRB in place in a CLIA laboratory to begin looking into that kind of work. But so we can play with cell lines. We can't we can't we don't have all the right regulatory structure to be working with consented human DNA. But there are researchers out there that are Phillip buckles is one who's put out an offer to sequence anyone's tumor to look for this stuff. That Probably the place to look, I don't think you're going to find this. If you just go fishing randomly through someone's genome at a random tissue per se, I think it'd be better to focus the effort on a tumor type that's evolved postvaccination be great if if anyone has had had a tumor, let's showed up right at the site of injection, that's kind of an indication that maybe the vaccine is causing it. And that would be an ideal tissue to sequence. So those studies are ongoing, there are folks that are pursuing them at the moment. This this cell line thing is simply meant to be a model to get us more information about what could be going on with the vaccination processes it can get in there, it may be a proxy for what someone who's in remission may experience post vaccination, you have to you kind of have to remember that we are always canceling, it's when our immune system falls down, that the cancer is emerging to be problematic. Normally, our immune system is clearing ourselves of cancer cells daily. And you need to you need sort of a multiple hit hypothesis here to weaken your immune system and increase the mutagenesis rate in order for these cancers to outpace the immune system. So you might, you might be able to view the the ovarian cancer cell line as a proxy for what might happen to an ovarian cancer patient who's in remission. postvaccination Can any of their, their their cancer cells, reemerge postvaccination. But it's not a person. And it's not meant to, we're not here to say that this is the perfect model for estimating it's the right thing is to eventually do this in humans. But before you go and do this in humans, you need to work out some of the methods first on cell lines before you just start doing fishing random fishing expeditions inside patients tissues, it's just a this is this is that step of the process of sort out the techniques and the methods, we need to do this so that when we do approach patient tissues, we can do it very efficiently. And we're not trying to learn on the fly with patients tissues.
Nick Jikomes 56:50
So it sounds like tell tell me if this is accurate? It sounds like you would say it's been demonstrated convincingly and replicated that for these mRNA vaccines. There are remnant pieces of DNA from those plasmids they use in the production process that make it all the way through and into the final product. Yes,
Kevin McKernan 57:11
yeah, that's that's been replicated by many labs. The the work that I just spoke to you about regarding treating cell lines with has only been done with ourselves and only I've heard of one other lab that's that's seen it as well, did a result call that saying he's done similar work. And he's is he seeing the DNA going into the cells, but neither of us have published anything more than a subset.
Nick Jikomes 57:33
So that work that tell me if this is a fair summary of that work, that work shows that, in principle, it's possible for some of this random DNA to persist inside of cells and be replicated a number of times to potentially mutate and potentially even integrate into the genome of, of the host cell. And that means it's at least theoretically possible that could be happening with the mRNA vaccines and people but it does not prove that it
Kevin McKernan 58:02
does not prove it. And I also caution that so the PCR work has been replicated by many others independently, the the cell line work that we just spoke about has not yet been replicated by other people. So it's much more nascent. There is some, you know, word of mouth that we've had, you know, sharing with other colleagues on this, that they've seen it as well. But all of this needs to get kind of summed up into a into a paper that we'll read shortly submit. So there's, there's more replication that's needed on the cell, treating the cells with a vaccine, and what happens is really fresh, fresh territory.
Nick Jikomes 58:32
What does all of this start to say about, you know, this is new technology? These are mRNA vaccines different from vaccines that have been historically used? It's a new type of technology, due to the COVID pandemic. And you know, we all probably remember the early days, how much uncertainty and how much panic there was, you know, we wanted to rapidly deploy technology like this as quickly as possible. How does it start to get you thinking about, like weighing the pros and cons of, okay, we want to, we want to scale up and rapidly deploy this type of new technology, which looks promising, in many ways, against the fact that it's new technology, and we don't know all of the little quirks and things that are yet to be discovered. Yes.
Kevin McKernan 59:13
So maybe COVID isn't the best analogy for this just because the IFR and it is so low and kids that I don't think they necessarily warrant this type of risk. But there there's terminal diseases out there that perhaps I mean, I know Alan islands out there with they have an RNA that they use. It's not does not come from a plasmid. It's a very short interfering RNA, which is like maybe a 20 to 30 base pair piece of RNA that's chemically pure, they put into SNPs. And they infuse into people over eight hour drip under immunosuppressants. So that's a very different approach of using RNA. And I can't speak to how well it works. I've just not heard of these really strange adverse event profiles that we're seeing on the COVID vaccines and that's also being utilized for a terminal Disease. Alright, so they've kind of found a disease where the risk benefit ratio is obviously very different than this respiratory virus. Their administration is being done much more carefully through infusion with immunosuppressants over long periods of time. When you turn to the COVID vaccines, we have a large class of people that don't need them, a large class of people that are already have natural immunity. And we're taking very similar Gamble's without having the same precautions in place, we're not infusing these over periods of time with immunosuppressants like they're seeing, like they're using with these other other drugs. So there's, they're very different. I know, people want to like cast stones at all RNA and kill it forever, I'm not of that mindset, and that there are applications that don't have these manufacturing defects that seem to be in the marketplace that don't have a there's, you know, explosion going on, that I'm not willing to, like, condemn, because there might be a use for this in some discrete circumstances in healthcare. So. But in terms of COVID, I'm just perplexed at the, the biology here, I don't understand why we're trying to build immunity through injection, most of these viruses enter through your mucosa. And it's very hard to get mucosal immunity through injection, you build antibodies in the wrong compartment of the body. So so maybe they protect you, if the if you had viremia, and the virus went everywhere and into your bloodstream, they then they would turn on but by then it's kind of too late. You really want respiratory immunity in your mucosa not Not, not an injection. So I think it's the wrong platform fit if you will, for for respiratory viruses. Set aside all the purity issues, if they perfectly cleaned everything up, you have to ask yourself, Is this the right way to stop a respiratory virus and has to be really, you know, I think, a very virulent virus for you to consider it given the unknowns that are involved. So you know, I'm not here to condemn the whole platform, if they can clean up the manufacturing and find some type of use case where the risk risk benefit equation is very different than what we've been presented with. And they may make sense, but I'm having a hard time finding that and anything related to a respiratory virus.
Nick Jikomes 1:02:18
What are the vaccine manufacturers like doing this type of work to clean up that process as the work that you've described, that you've done, prompted them or regulators to tell them that they need to do some more stringent testing and just streamlining of this process?
Kevin McKernan 1:02:35
I don't know that it has, I mean, there is their prep app gave them additional liability protection, my understanding of the prep act is it extended the liability protection to beyond the pharmaceutical manufacturers and even to the administrators of the product. So the nurses and the doctors are administrating these things have some shield over them as well. So in absence of liability, I suspect they are not financially motivated to do anything. And the signaling we're hearing from the FDA is that there's nothing to see here. They the manufacturer claim they tested this, we trust that they did so we're going to take their word for it. I mean, I What I'd love to see are the are the regulatory agencies actually performed some PCR because I think when they do that, they'll recognize that the numbers are higher than what the manufacturer promised them. I mean, the highest slot we've seen yet came from Germany, it was at a CT of 13. So for those familiar with PCR, you may even call positive at a CT of 33. For the virus outside of your nose, that's a 20 ct gap by a million fold gap. So there's a million fold more of this contaminating DNA being injected, then you might get called positive, or remnants of virus that are outside of your nasal mucosa. Not inside per se. So that's a that's a large difference to be concerned about. So they're probably thinking the CTS on this are out in the 23 range, which is where they should be if they're below the below the guidelines 20 to 23 range. So I think they're, they're putting a little bit too much faith in the manufacturers measurement of this there should be independent measurement of this. And the techniques that are being used should be published. This is one thing that has concerned us is the techniques we see looking through the EMA documentation shows that they're allowed to measure the DNA with qPCR, which is very stringent and under measures it even according to Madonna's own patents, but then when they go measure the RNA, they can use fluorometry, which will over count the RNA. We've put some of this in our preprints. But those the fact that they're measuring these things with two different yardstick shows you there's a game going on, because anyone who's done PCR or 10 of COVID tests for that matter knows that you can measure DNA or RNA with PCR. So if you're asked to be measuring both, you should be using the same yardstick for both not not playing this game of I'm gonna inflate the RNA with one technique and then use this PCR method to deflate it and another tech So I can slip through the regulations. So there is there is a bit of a game going on as to how they're being held to these regulations. So I'm not surprised the regulators are confused by this other, they may not be, you know, alerted to the fact that the techniques that are in play here give you vastly different quantities of RNA and DNA, if you're given the freedom to cherry pick the tools.
Nick Jikomes 1:05:23
Let's talk about spike protein itself a little bit. So the intended way these vaccines are supposed to work is the mRNA encoding a spike protein gets into our cells, our cells use that to make the spike protein itself from that mRNA. And then they are presenting that spike protein to the immune system. And that triggers an immune response. And that's, you know, that's how we generate immunity from these mRNA vaccines. Last time we spoke, we were talking about how when you look at some of the data that's out there in this documentation, the western blot data, it sort of looked like when you look at it closely, and you know how to look at the stuff. There wasn't just native spike protein being produced. But these these bands were smeared, implying that there were various variants of this protein being made at some frequency. And we were speculating that might be due to this frameshifting thing that can happen with this modified uracil. nucleobase that's used, that we talked about earlier. And since then, and at the end of 2023, there was a paper showing, in fact that you do get this ribosomal frameshifting. Can you summarize that for people? What exactly did they find
Kevin McKernan 1:06:28
there? Yeah, so these bases, when the ribosomes are going across reading these bases, they read them in sets of three. And you can imagine if you change one of those bases, and put a methyl group on it, that it may confuse the ribosomes capacity to translate that codon into the right amino acid. And that's in fact, what that Mulroney paper is showing is that in particular, when you have three pseudo yearlings in a row, the ribosome gets confused and slips on it and goes off by a frame. And then it starts reading the RNA transcript, one bass out of frame, which is entirely different language, and that and make spurious peptides after that point. So that is what the Moroni paper demonstrated, I think that's half of what's going on the other. The other concern that can happen in making these RNA templates is the same bases that are difficult for the ribosomes to read, are sometimes difficult for the polymerases to read. And there's something known as template switching that has gone on. And that's at least in Madonna's own documentation. So they're very scrupulous at looking at how much double stranded RNA is in these things. And they even published a paper showing that they mutated T seven polymerase to make it to stop doing this, this template switching. So what is template switching? Everyone confuses that with frameshifting. But template switching is when the RNA is getting made. And the enzyme falls off. And it's not completely made yet. And then the strand hybridizes to another strand, and it starts copying in the wrong place. Alright, so it switches to there's two forms of templates switching, there's trans template switching where the template lands on a different part of the DNA molecule and Prime's off of that and it's and it's therefore making A chimeric template. And then there's sis template switching where the RNA loops back on itself, and goes the other direction. That says template switching is called, like loopback extension or loopback, extension or loopback. polymerization. So Minerva has this interesting paper showing that when they mutate a piece of polymerase, they can eliminate a lot of this template switching. You know, the problem is that paper came out in 2023. And it's not clear to us that they had that operational when they were making the vaccines, neither Pfizer or Madonna, for that matter. So what that can mean is that you can have some RNA templates that are that are not correct, they've they've kind of part of it's correct, and then hopped, hopped onto another piece of DNA and hybridized there and started making more, making more RNA, that's not correct, that chimeric RNA, if you will, or loop back on itself and started making more RNA, both of those mechanisms would can create RNA that's longer than the expected length. And that is something that we see in some of their, their plots when they when they look at RNA integrity scores, they run these things on electric reset system, you should see a really discreet peak at 4284, which is the length of our mRNA. But in fact, what they see is a smear before and after that RNA, which is a sign that there's longer transcripts in there and shorter transcripts in there, and those could lead to other types of proteins, if you will. So I think Maroney did a great job showing the frameshifting is, in fact happening with the ribosomes and translation. But there's another layer deeper than this that I think has been harder for people to pin down, which is is it what's the degree of template switching and double stranded RNA that's being made in this process? Now, in the case of the Pfizer vaccine, I'd be more worried about it because the Pfizer vaccine, the opposite strand on the Pfizer vaccine doesn't have any stop codons. So if you do get any loopback RNA extension on Pfizer, it's going to make a chimeric peptide for a very long time because that piece of DNA has has no stop codons in it. So if you get a loop, a loop back, Trent mRNA, you feed it to the ribosomes, it's going to keep making amino acids until you know till the end because it has no has no stops built into it. So there's there's a particular I think unique issue for Pfizer with template switching because they're codon optimization eliminated all the stop codons and the reverse strand. And that means that there's an open reading frame that's undisclosed in their vector that is not presented to the regulators. The regulators demand that you have every open reading frame disclosed in a product like this, and that reverse, or has been omitted from any disclosure to the BMA or the FDA. So,
Nick Jikomes 1:10:49
so, the Mulroney paper that looked at ribosomal frameshifting. That was in vitro, right. It wasn't in it was showing that this happens in cells. I thought
Kevin McKernan 1:11:01
they actually had patients in there. It was a small number. I thought they were I thought they were pulling that out of maybe maybe there were patients cell lines that they derived that to say that it's a good question. I gotta go back and read that and oh,
Nick Jikomes 1:11:12
no, hon. Yeah, I have the baby right here. ribosomal frameshifting In vitro and that cellular immunity in mice and humans, two plus one for encrypted products from the Pfizer vaccine mRNA. translation occurs after vaccination. Yes,
Kevin McKernan 1:11:27
there we go. Okay, so, so 8%, or something of the proteins they were mentioning in there were frameshifts did. So. Okay, so
Nick Jikomes 1:11:34
what's the punchline here that when these mRNA vaccines are used, you're producing native spike protein, but you're also producing a small, maybe a dish percentage of other variants on that spike protein that are not exactly the same?
Kevin McKernan 1:11:49
Yes. And we don't question. The question mark, if
Nick Jikomes 1:11:53
they're harmful, man is,
Kevin McKernan 1:11:55
hey, maybe that's, you know, maybe that those aren't harmful. But But I think to your initial point was, how is this different from manufacturing a peptide and injecting a traditional vaccine, you not exposed to this risk, because they presumably purified the wrong proteins out of any such thing that would occur, there's no pseudo uranium involved in those things. So the frameshifting should be a much more frequency. So traditional antigen that you inject wouldn't wouldn't have this, you're not playing games by trying to camouflage the RNA, get your cells to make it, trick them into making it and then exposing the cells to, you know, Miss translating these things?
Nick Jikomes 1:12:32
Yeah, so I guess, in inherent part of using mRNA, to make your antigen to make the protein that your immune systems can recognize is that really an inherent part of this process in ourselves is just noise, like there's going to be some noise, there's going to be some infidelity that the system has, and how much it happens is going to depend and whether or not it actually matters in the end, is still a question mark, but it opens up this possibility that things other than what you intended are now going to be inside of your cells. Yes.
Kevin McKernan 1:13:05
Yeah, I think that's something I've learned in building DNA sequencers is that when you modify a base, all bets are off. I mean, it changes the way the sequences read them, it changes the way ligase has handled them, it changes the way the polymerase is, and then like, as simple people, because just a methyl group, no way changes all the dynamics in terms of the melting temperature of those bases. It's, it's a complicated system. And nature has evolved these little signatures on basis for a reason because they hitch onto them to perform certain biochemical events. So decorating an mRNA with 100% of these different bases, is not something our cells have seen before. So it's we're in an unknown territory as to how the cells going to respond to those things.
Nick Jikomes 1:13:51
You know, when you think about all of this, molecular biology, you know, all of the details and complexity here. How does that influence how you think about the landscape of, you know, potential vaccine induced side effects and things like that, like that people argue about this stuff, because it's a highly politicized area, you know, you're seeing different things at different rates in different populations. You know, obviously, people have talked about the the myocarditis carditis issue. How do you think about all that stuff in the context of what you're learning as a molecular biologist? I'm
Kevin McKernan 1:14:22
a little bit biased here, because I spent five years doing mitochondrial sequencing. And so what really unnerved me about the Pfizer vaccine is that after the stop codons when they have in the mRNA, they have a five prime UTR, an open reading frame and then a three prime UTR. Those are on UTRs are these untranslated regions. So they don't they shouldn't get turned into amino acids, but they are in the transcript of the RNA. So the the ribosome was supposed to start at the start codon and Aug likoma thymine, and then keep translating until it hits stop. Hold on. Now in the case of Pfizer, they put in multiple stop codons because they know when pseudo urien isn't a stop codon, it sometimes doesn't behave as stopped going on. And it can frameshift. Fernandez has work showing that Fernandez had also paid for that we referenced in our preprint with Peter makalah, showing that when ribosomes read pseudo yridians, they sometimes frameshift across stop codons. Now what's so what's after the stop codon, and Pfizer is a mitochondrial sequence, a human mitochondrial sequence. So for making any, and if we're slipping through that stop codon and making any human mitochondrial peptides, I don't know what that's going to do. I don't know if that's going to make the spike localized to mitochondria. I don't know if it's going to going to trigger some kind of immune response against a mitochondria which I don't know how that would happen. They're intracellular organelles. But it's to me, that's a red flag, only because when I read about a lot of the people who claim to a vaccine injury injury, I see things I saw the mitochondrial space, I see pots, I see dysautonomia, I see brain fatigue, or brain fog and chronic fatigue syndrome, and all of these things that were showing up in the mitochondrial disease base. So I be, I'm really curious why they have that. They claim they put that mitochondrial sequence into to make it express better. And once again, they're trying to step on the gas to make it last as long and as powerfully as possible. But that's not always the right approach and pharmacology to have, you know, everything on it full blast. So I would be worried that there could be chimeric spike human peptides in there, which could create autoimmune issues. So I don't have any proof of this, I just see the spectrum profile of patients out there that that are vaccine injured, and that seems to be very Mito based. And then I see that there's mitochondrial sequence inside of the Pfizer vaccine and wonder what happens when you frameshift shift into that stuff? And does it does it create these, these chimeric peptides?
Nick Jikomes 1:17:02
Can you talk a little bit more about the persistence of the spike protein? What does the literature say out there in terms of how long spike protein produced from the vaccines is actually lasting in the body? And is that? Yes, so what we think is it what we thought it was originally?
Kevin McKernan 1:17:16
Yeah, it's not what we thought it was originally. But there's several there's two different avenues here, there's the nucleic acid longevity, which right now the day we have shows that shorter than the actual protein and, and some of that could be measurement technique. And and, you know, the number of studies that have looked for both, but so on, on the vaccine front, we've seen krausen at all, demonstrate in the heart for 30 days, we've seen cast for you to show it in plasma for 28 days. Now. We've seen Hannah show it in two different studies from Hannah at all, in the breast milk, five days or more, there's a lot of critiques that there's that these, these these numbers are such small numbers that they don't matter. But I've have some subsets that go through those numbers. Some of the issues with the first Hannah paper was the PCR test, they had only had a LOD at 440,000 molecules. So it really couldn't see it out to 30 days because the PCR test was several orders of magnitude insensitive for the job. There's another paper recently, I'm going to murdering the last name, it was in placenta. And they demonstrated one patient that was vaccinated two days before birth and one vaccinated 10 days before birth, and they picked up RNA in the placenta. Now, most of the papers looking for RNA right now aren't really splitting hairs between RNA and DNA. So we don't really know if this is an RNA or DNA issue, because when you do RT PCR and amplifies both, and most people, I think we're assuming these vaccines had no DNA in them. But you have to go back and revisit those studies with some nucleases present to sort out whether it's RNA or DNA. But so that gives you a window about 30 days, okay, somewhere between, you know, those studies went from two days to 30 days. On the nucleic acids. When you start getting involved with the spike protein itself, we have the Bansal paper that showed that it was an exosomes, I think that was more months out and forgetting the author name, 187 days was the longest one, I think I've seen unshown spike protein in which is namely that they might come to me later, but there's a there's, I think I have a link to it on my stack for for the spike protein. So we're seeing the protein sit around longer. Now, a lot of people point to Well, shouldn't the immune system be clearing out the spike? Why is it sitting around for so long? And there are a class of cells in the body that are amino privilege cells like stem cells that your immune system won't clear out? So if the MPs get to stem cells, that could be one source for why there is a spike. That is evading clearance. And
Nick Jikomes 1:19:51
so, yeah, so if the LMP is get to those cells, how might that happen? So, you know, I've heard people talk about, well, we're getting these injections into our arm. They're meant to be like intramuscular. Alright, but you know, some percentage of the time, right? It's going to hit an artery or a vein and get into circulation. And I guess the concern would be, if and when that happens, and it's inevitably going to happen some fraction of the time that in those people in which it happens, those MPs are flown all over your body and maybe getting to other places. Yeah,
Kevin McKernan 1:20:20
that's, that's the best theory I've heard is that, yeah, accidental, because and this will probably explain why like, not everyone's getting sick with these vaccines, there seems to be a sort of stochastic nature to it, where a lot of people taking these and they're fine, they've experienced no issues. It's just a subclass of people. And maybe there's a another confounder here, which is certain lots from from our study, the lots they vary. We've seen stuff that's very, like 10 cities, there's 1000 fold variants in, in the amount of DNA contamination that we've seen, just surveying maybe 30 or 40, lots. So you could have people who are bad lots that are getting a lot more of that contaminant, you could have people on top of that, that it's, you know, it's staying in the arm, it's contaminated, no big deal gets into the circulation goes to all the cells, and now you have a transfection experiment with contaminating DNA across all the cell lines. So there can be a combination of these things, it gets very complicated. But I do believe that there's, there is some stochastic nature of the injury, right? Not everyone is hurt by these things. So we have to keep in mind that maybe it's only the people that get get hit hit in an artery where this thing causes problems. And some people may get hit in an artery with fairly clean lot. And it's not an issue either. So there's, you can't use the fact that there are billions of people injected to say that there aren't there aren't people getting hurt by these, that I get that all the time online that these are safe, because billions of people smoke cigarettes, you know, and it's like, now, if you're not counting the injuries correctly, that's not a fair way to go about assessing the risk here.
Nick Jikomes 1:21:48
What do you so the myocarditis pericarditis issue, my read of that literature is that it depends on demographic, right, there is an age and sex dependency are and basically younger males are at higher risk, the absolute risk is relatively low, right? It's like one in several 1000 males under the age of 20. Something will get myocarditis. But it's much higher than than chance would predict. What do you make of the age and sex dependence there? In the first place? Why would something like this depend on the demographic you belong to?
Kevin McKernan 1:22:21
Yeah, it's a good question. I just heard a podcast from Steam in any coca on on Jay Bhattacharya is podcast. I think the illusion of consensus where he was going through some of the studies that were looking at myocarditis caused by COVID, which he wasn't very convinced of is the studies had a lot of a lot of flaws in them. And he walked through some of those flaws, but the ones from the actual vaccine have some real hard clinical evidence through autopsies. And through looking at with with MRIs, and looking at troponin levels. You know, I don't know why it's hitting males more than females at that young age demographic, he was bringing up androgen and other types of hormonal issues that might be at play. So that those are, that's not my field of expertise. So I can't comment very, very effectively on that. But I do that was a good podcast that walk through that that's worth anyone who wants to dig deeper on it.
Nick Jikomes 1:23:18
When you're doing, like the research that you described, in this area, you know, given how much controversy there is, when it comes to some of this stuff, how intertwined this whole area is, with politics and stuff. How has it been trying to publish work? And I don't know, is there anything interesting going on there? Is it is it more difficult to publish work? I mean, it definitely seems like right, there's there's lots of motivating, motivated reasoning going on. There's a lot of people who want to prove this who are want to prove the opposite. What's What's it been like doing the research and trying to get it published.
Kevin McKernan 1:23:54
So we haven't been very successful getting it published, that the first one we put out with Peter McCullough, that describe this frameshifting had two reviewers approve it, and then the editor swept in and killed it in some very curious way. But lo and behold, the frameshifting turned out to be pretty well forecasted.
Nick Jikomes 1:24:17
You submitted a paper to reviewers looked at it the normal peer review process a couple other scientists and anonymously review the paper. They said, go ahead and publish it. And then after that the editor, the person above them came in and said, It's not we're not gonna publish it
Kevin McKernan 1:24:30
or not to it. Yes. Now, what was the reason? It was at Hindawi. And they didn't give us a good reason. That's what was really frustrating. And I did notice after we received that, there was a notice that Hindawi was like retracting, like 500 or 1000 papers, that they had gone through some investigation. So I think they were under probably extreme scrutiny at that time, going through this process of, you know, retracting, 500 papers, so we may have hit them at a bad time, where they're like alright, We're just not taking any risk right now because we're in the process of doing this retraction. But they didn't give us a reason for it. They just they just said, No, we're not, we're not moving forward with your, with your publication. So we ended up saying, Alright, it wasn't as clear as that, to be honest, they were like, they just kept dragging it out saying, we're not we're not, we need an extra review on this. We've graduated your paper to go to another tier of review, because, you know, whatever, for whatever reason, and we just got tired of them and said, Listen, this is taking too long, we're gonna go somewhere else with it. And that's kind of how things were left with and daily. But so that was a case of and that was that wasn't even a paper with a whole lot of experimentation. We just did some bioinformatics analysis on the number of like, quadruplex G's that showed up in this and a couple other RNA fold issues that were that were somewhat interesting. I think the interesting one interesting detail on that paper was that there I don't know if you're familiar with this Andy fire paper that came out recently looking at obelisks, which no, so it's really fascinating work that they found they went they went combing through the SRA looking for double stranded circular RNAs. And and I work in that field with fibroids are double stranded circular RNAs, but they don't code for anything. And he found a bunch that are about 1000 bases long that actually have an open reading frame, and they're circular. And they're hairpins. And they're so their new new like chemical entity if you will, known as an obelisk that they coined, but that that paper led me to one that shows that the mRNA folks are designing their codon optimizations to be very broad like because those are harder RNAs to destroy, and they last longer. And I hadn't known I didn't know that when I wrote the paper that makalah because I know that I did see that they made the all the RNA code and observation made them hairpin a lot more. And I was just shocked at the secondary structure change. When you put the code on optimized RNAs to RNA fold, you see all of these hairpins that aren't in the actual virus. And then that that anti fire paper came out linking to a group that said no, when we, when we code on optimize for mRNA vaccination, we try to turn them into rods, because these hairpins protect them for degradation so that it was mostly an in silico analysis with Peter McCullough, and a bunch of literature searches around you know, what could go wrong. So there wasn't a whole lot of stuff to critique other than, you know, we don't like the collection of citations you put forward here. So most of the reviewers were like, Yeah, this looks good. You've all these are real citations, and you know, the paper sound. And then I think Hindawi got stuck in this. Okay, we're in a retraction mode, now of, you know, tracking a bunch of papers, we're going to put all papers that are controversial through a secondary screen again. So I think that's what that one got caught up. But since then, this work, having had that experience, we just went with the approach of put this stuff public as quickly as possible and do the extra work in the lab to make it easy for someone else to reproduce it. Like it's one thing to make a paper, knowing that someone's going to peer review without a pipette, it's an entirely different matter to say, now we need to actually build additional assays. So someone can pick up a pipette. And reproduce this, that's a whole nother month of work, which we did on this, when we put out the work with sequencing the vaccines, we didn't stop at just putting the sequence public. We want to design quantitative PCR assays that targeted three parts, the plasmid fine tuned all that stuff, but the primers public and that enabled, you know, many other labs to just pick up the primer sequences and check their vials for like 100 bucks instead of having to sequence the whole thing and sort it out. So if you're gonna go this route of, I think being very transparent, you have to put more work into not necessarily thinking someone's going to just read the paper and double check it, but anticipate someone to have to replicate it at the bench and do the extra work to make assays that afford that and make it easy for for replication, because you're at that stage not relying on reviewers blessing this. Reading it, you're relying on the field replicating it at the bench. And I think that's a faster way to go. Because because I don't really care about peer review. I care about replication. And the moment people start pipetting, you get better feed back. Like when Philip did this work, he pointed us, you know, he pointed to a few things that we missed. And when suddenly did some of the work, he taught us things and David's speaker taught us a few things, right. So the pipetting is the real review. And that's where we actually sharpen the pencil quite a bit. So it is politicize it is difficult. But I'm losing faith that the system we have isn't isn't like, captured in consensus building and that it's hard to publish something that bends the narrative. The system is very much narrative reinforcing the current peer review system. And if you're outside of that, you're probably not going to have a good time with peer review. It's probably going to take it here and you might want to consider going with a preprint with that has a hell of a lot more effort focused on how does someone get the lab reproduction done as cheaply as possible
Nick Jikomes 1:30:00
In your mind, like what like when you're reading papers, if you're looking at a preprint versus something that has become, you know, an official quote unquote paper that's gone through the peer review process and gets into a major journal. How much does that? How much does that matter to you do? Do you think the the pre preprints are less worthy than the ones that make it through peer review? Do you think that doesn't matter so much at this point,
Kevin McKernan 1:30:26
I think what happens is for me, I'm if it's in my field, I go right to the Methods section and look at the conflicts those the if I can understand the methods, and the results, and the conflicts look clean. That's all I care about, I usually ignore the abstract and conclusions, because those are usually marketing things that you put forward to the journal to make them interested in publishing it like this is a story that has great significance for X, Y, and Z. And they're oftentimes not necessarily evident in in the results, right, people can look at results and interpret different things out of it. So if you're, if your set of authors who is in the world of like, these vaccines are safe and effective, you will see a set of data and be like, this shows that they're safe and effective. Another person could see the same data and be like, I don't, I'm not so certain I view it differently. Right. So conclusions are always there's always a subjective nature of conclusions of the author's interpretation of the data is embedded in the conclusions, whereas the results in the methods themselves really tell you everything you need. So in my own field, I don't I don't discern between whether if something has been published, whether it's a poster or whether it's on a preprint, because I can decipher it, when I get outside of my lane, I then have to rely more on other experts. And I'm easier fooled. And I tend to read into the the abstract and the conclusion is a little bit more than I probably should. So that was a I, I think the most important thing if you're outside of your wheelhouse, is that you scrutinize the conflicts first. And if there's a lot of conflicts there, such as this is funded by Pfizer, and I'll be like, Okay, I don't have time in my day to read Pfizer paper, it's gonna move on to one that doesn't have conflicts. So I tend to put a lot of weight on the conflict of interest section only because I've seen so much of that in COVID, where the results of our have sponsorship like that, and they're just polar opposite of what I'm seeing from from like physicians on the ground, and what they're telling me that I can't take a whole lot of faith in the, in the peer review system, giving faithful information in that direction. And I think it's more of a concern for me when the sponsors are very large financial institutions than small ones, because they have the part of the person the capital to actually advertise in that journal, and to influence perhaps the way the editors are behaving. And many people may not know this, but the the way the financing of peer review behaves is the people who want to publish give the journal about $3,000 hand over their copyright of their material to the journal. The journal then makes money, not only by receiving your $3,000, but by also doing advertisement for folks like Pfizer inside the journal, and then reselling access to the copyright of those things to Harvard and Stanford and what have you through they put these things behind a paywall, there's like a 35 to $50 fee for someone to download the paper. So there's a there's a risk there that the intermediary, the Oracle, if you will, running the journal, can be influenced by their advertisers. And I certainly think that's what's happening in the mainstream media. It's probably less obvious in the actual journals themselves. But mainstream media there's like, every single basketball game I watched now has Maderna on the floor and brought to you by Pfizer. And and they never say a negative thing about the vaccines. And the journals, I think, to some degree, this may be going on as well, that they are very pro vaccine, they've always been pro natural origin of this as well. So there's been a lot of protectionism of a particular narrative through the journals that I don't think is really welcoming of people who have counter narratives. So you know, we're trying to break that there's a couple of people I know that are trying to build a peer to peer review system where it doesn't have a journal involved. It's just a capacity to the Publish, and everything gets etched onto blockchains. And you recruit reviewers in without a journal. We'll have to see where that goes. But I think that's a I think that's a better system, just because I do think the review system, since the review, the people who are adding the most value to review aren't getting any of the rewards. So there's no reason for me to do a peer review. I don't get paid for it. It just takes away from my day. And so the only time I would that I find people jump into peer review is when it's in a field and they're worried about competing work, obliterating or scooping there's and not that many people are going to be not not many experts, can you get a lot of time for free and that's what the journals rely on to getting experts to come and review the stuff for free. Then I think the incentives are broken. I think if you put a put a bounty out there for reviewers and it was very transparent. You'll get people to instead of driving Ubers, on weekends, PhD students can be reviewing papers and getting paid better than they might be gaining an Uber salary, if you will. So I think we can change peer review, if we put in market incentives in place and turn it into a more of an Austrian economy, if you will, where there is pricing signals and peer review and you can get platinum review, Gold Review bronze review, you can get fast review, slow review, you know, five reviewers to reviewers. Right now, it's a very one size fits all review system. And there's no urgency involved. I have a sub stack from just this weekend actually about a peer review in the philosophy space that I went through that took three years. And it's it's just a total train wreck. If you read through through it all. There's no motivation for anyone to actually review things quickly. So I encourage people to read that if they want to get an understanding of how that sausage is made, but I think it's time to disrupt it. We saw too much of this in COVID where surgery sphere came out proximal origins came out all of these papers that massively disrupted the patient access to hydroxychloroquine came through and they were later shown to be frauds. So the system doesn't have a very good reproduction rate and reproduction is where we should focus.
Nick Jikomes 1:36:20
Did you see what happened recently with the FDA and some of the ivermectin content they produced? What what happened there? Exactly. And what's your take on it?
Kevin McKernan 1:36:29
Well, they did step out of their lane they started mocking people using ivermectin and it's not FTAs charter to prescribe medicine. Alright, this is a even with physicians, they get nervous prescribing medicine to patients they've not met or looked at us. It's frowned upon, right? You should at least have a telecall a telemedicine and you know, poke and prod the patient a little bit. But the FDA started saying ivermectin is we're not horses, you know, stop it, y'all. And ivermectin. And so you look at that behavior, like they are becoming a marketing engine for the vaccines. Why would they pick a fight on which product that they want to support or not support? You know, ivermectin is a Nobel Prize winning drug that's already been through the FDA, but it's no longer really protected by any IP. So it doesn't have it's unlikely anyone's was going to put ivermectin back through the FDA process and pay them again. I mean, the FDA operates off of the Paducah act, where about over half their budget comes from pharmaceutical companies, paying them to defray the costs of regulation. So unless you're, unless you're in their pay stream, they're probably not protecting your drug. And ivermectin is something that fell off patent and no longer really has a protector like that, or sponsor, if you will. So they seem to be shooting down generics to, you know, art, the Red Sea for the people who are paying them for the most latest and greatest drugs, which are, of course, the most dangerous drugs because we know the least about them. So it's, it kind of works against generics in many ways. And I think that was a perfect example is good to see Mary Mary succeeded in getting them to reverse it, I'm, I'm only worried that they'll do it again, right? They got a slap on the wrist, they have to take their posts down and that little bit of a, you know, a humility session there. But they're not necessarily. If it takes three years for you to reverse something like this. They're going to do it again. And then we'll have three years of the courts fighting them to stop doing the behavior in the future. So I'm not convinced what although it's a victory, I don't think what came out of that is going to prevent the behavior from reoccurring.
Nick Jikomes 1:38:44
You know, given how much controversy a lot of the stuff is embroiled in, you know, how politicized everything to do with COVID and vaccines and ivermectin and other drugs, how it's what a mess. It's all been on the ivermectin issue. When you step back, and you look at all the evidences out there. There's obviously right there's a lot of good and bad studies published some of them wanting to prove one side of the equation, some of them wanting to prove the other. What's your general read on? The truth regarding ivermectin?
Kevin McKernan 1:39:13
I'm probably biased because I follow Pierre quarry and read his stack quite a bit. And it looks to me that it works. Now. I'm also coming from this from a medical cannabis world, right where I'm like, It's not anyone's business, what drugs people take, if they think it's going to help them, let them take that. And so this is one of those scenarios where they got and they got in the way of a drug that won the Nobel Prize in Medicine. And it's clearly has low toxicity, otherwise they wouldn't approve it for all the other things they use it for. And they're able to railroad it in favor of some other therapeutics that had had better royalty streams going into the government. Right. There's a $400 million royalty stream going into the NIH for for Maderna. I don't know how much is coming in from Pfizer, but I'm assuming that Pfizer is probably going to be paying them eventually as well. So others, you know that the government institutions are all cheerleading for the thing that probably fills their coffers the most and trying to shut down anything that can reverse that or challenge that. So I don't understand this. It was never a crime to to put drugs or to use drugs off label until COVID. Right. But
Nick Jikomes 1:40:18
when you say you think that ivermectin works, what exactly does that mean? Like, what dose use for what purpose? In what way does Oh, yeah. So
Kevin McKernan 1:40:26
the the most people who are using ivermectin aren't using it alone. And a lot of the studies that attacked it, use it at doses that were inappropriate. So they're usually using it with like, like a Z Pak, maybe zinc and ivermectin like that, at least the those three things. And they're showing I think the most recent one I saw was somewhere like in the 70, or 80% reduction in, in mortality with with ivermectin. And now it has to be given early, you know, some of the studies would would test this in hospital, or at least with hydroxychloroquine, they pulled that move and hydroxychloroquine, where they tested it after only they were blue in the face and practically dead, and it gave them a bunch of you know, hydroxychloroquine, and it's not going to work at that stage. So there were a lot of trials that looked like they were set up to tarnish this with doing all types of games with the placebos and the controls and dosages. I think the last thing I read about ivermectin, it was somewhere around 150. Was it micrograms per, per kilogram or something. So I don't have that I'm not the best person to quote on there, like the optimal dose here. I want people to pierce work. He's got a whole book on this. But the few papers I've read that he's put out, and his sub stacks of all pointed to the defects in the trials that we're trying to take this down the connections to pharmaceutical sponsors, and and then the less conflicted trials and the results that they saw. And it seems to lean in the direction of this working. And the fact that we have to do all of this at all seems ridiculous because they it was legal to prescribe off label drugs for for this before the pandemic. And then we had to do all these damn trials just to fight over whether they could have the rights back. So I get I get I get a little bit frustrated, because I'm, I think you have some probably some similar background in the medical cannabis field as well, where these these products are going to be hard to get clean trials on, we have entire government agencies trying to take them down like NIDA, that likes to do studies that demonstrate abuse of drugs. And so it's hard for them to ever admit there might be a benefit in such a study. But we've got lots of patients that are that are demanding access, they believe it works. And that's that's where the I think the debate should end. But it seems like it has to get politicized and there has to be a fight over who gets to collect the revenue stream of various medications.
Nick Jikomes 1:42:49
I want to switch gears for just a little bit while I have you. You know thinking about cannabis. You mentioned very briefly at the beginning, something important that's happening in that world, which is this infection, which isn't decimating cannabis crops. What is this thing? And what do we know about it?
Kevin McKernan 1:43:08
Yeah, so this is hot plate and viroid. It's a 256 letter genome, which is remarkable. It doesn't code for any proteins. It's a circular RNA that when it gets into a cell, since it's circular, it can replicate with rolling circle amplification, but it needs the host polymerase to do that replication. And then once it makes a long concatenated genome, the bolded RNA oftentimes acts as a ribosomes and chops that RNA up. I don't think that's actually happening with hoplite. Android, I think it has a different mechanism, something else in the cell is probably chopping the genomes back up and folding them back into circles. But anyway, it tends to a lot of plants that tend to sit in the roots. And then when the plants go into flowering, it travels all over the plant and reduces the yield about 40%. There are some plants that seem more resistant to this than others are tolerant, I should say to others. So we still don't fully understand the biology, we think what's happening is the RNA has certain sequence homology to about 20 different genes in the cannabis plant. And through a process of RNA interference, it hypervisors that RNA, and that RNA gets clipped, or diced and cut into pieces. And so it's down regulating the expression of certain genes that also enable its capacity to replicate. So that's kind of the mechanism we think is at play at the moment. And there's no cure for it that we know of yet people are just if they detect it in a plant, they kill the plant. So there is a lot of PCR going on in the field where it's actually a very interesting economic use case because a grow can put into PCR system and start running PCR and see the economic gains of cleaning their grow and getting more healed in like less than a year. Which is quite different than the kind of sentiment that's been left in the field with PCR for COVID where we were, you know, probably quarantine Getting far too many people and everyone has a bad taste in their mouth. But with us, it is a prime example of being able to demonstrate that yes, PCR can can track down pathogens and in such a way that the cost of the PCR is more than made up for the reduction in the pathogenesis of the disease is trying to it's trying to sleuth out. How
Nick Jikomes 1:45:19
do growers detect this and quarantine and get rid of it?
Kevin McKernan 1:45:23
Yeah, most aren't quarantining, they're just if they if it's hot, they get rid of it. So you basically you take a either leaf punch, preferably a root, a piece of root because it's some plants, hide it in the roots, and it's not in the canopy. And you boil that for a little bit and then run it through PCR and an RT PCR will give you an answer. And we've got a system that doesn't like in 50 minutes, you get out an answer as to whether it's positive, not as positive. In most cases, they they just call the plants. There are a few like mother plants where people in the cannabis industry, they're not using seeds as much for THC plants that are grown indoors, because there's too much variability right now. And a lot of the seeds, seeds are siblings, so they're not all the same clones are identical to the mother. So what happens on an expensive indoor cannabis grow is a clone the mother plants, and that cloning process is cutting into the plant quite a bit and creating a lot of injury. And that's where a lot of the hot plate environment is getting transmitted through it's getting transmitted through scissors. So that cloning process can spread very, very quickly in a nursery. So there are some studies right now that we're working on that show there are genetics out there that seem to be more tolerant of this. So you want to be careful, if you put a program in place where you just chop everything down, that's positive, you may be chopping down some of the plants that you need to breed to get out of this. There are some plants that keep it in the roots, and they don't it doesn't go to the canopy, and those are probably the ones you want to start breeding with to build up a set of genetics that are more tolerant to this what what strains would those be? We've seen that in Jamaican lion, which is one that we've done a lot of publishing on it's it keeps it in the roots and doesn't spread to the canopy. Zamir Punja has a few strains as well. They're mentioned in his recent publication that had maybe only 5% yield loss and very rarely had it in the in the canopy as well. I don't know that I don't know the actual names of his strains there in his paper, but I don't even remember them offhand. So how,
Nick Jikomes 1:47:21
how big of a problem has this been for growers so far? Well,
Kevin McKernan 1:47:26
it's, I think it's more of an issue on the indoor grows, where there's a lot of cloning going on. And so we've heard numbers of 40% yield loss, we've heard, you know, probably a billion dollar of loss in California alone. People are getting better at this, those those reports are a little bit old. And they're not necessarily a peer review economic report. But they're getting better by screening this. And we now know that some of the places that are doing a lot of the cloning have to have better sterility and more bleach involved in the process. So once people have put molecular testing in place, they can get the infection rates down to almost zero, they just have to have an aggressive screening program, every time they bring new genetics in. There's a little bit of work going on with tracking this and seeds and then pollen, it does move in pollen, it's not as effective in the seeds were some lines have a higher percentage of seeds getting it than others. So there's, there's still a lot of work to be done on which genetics, you know, move more of this than others, I think we're going to find in time that some of them are more, the outfield went through this already, and they don't test anymore, because they've now got the lines that they need to do, basically, they know which lines are more tolerant of it, and they tend to grow those, I think I see
Nick Jikomes 1:48:44
so so people may sort of breed breed the problem away by creating plants that are more resistant. That's
Kevin McKernan 1:48:49
yeah, and that's an important point that if like if you have these plants that are positive in the roots, but they never move to the canopy and to kill those two, you might be killing the plants that we actually need to keep in breed. So I we will always recommend people test both leaf and root to know what kind of plant you have if you got to do it in veg and flower because in flowering, the plant changes and you end up getting more bioroid flow in some in some of the plants. But if you don't have it in the flowers and it's it's in the roots that may not be one mother mother plant you want to kill that might be when you want to put your breeding program because it seems to be keeping the fibroid contained, at least.
Nick Jikomes 1:49:28
Alright, Kevin, I've taken probably enough of your time here. Is there anything that you want to reiterate or any final thoughts you want to leave people with about anything that we talked about today?
Unknown Speaker 1:49:37
No, I
Kevin McKernan 1:49:38
want to thank you actually, for the time on this. I honestly think this is the people get a better sense of what's going on in the scientific field from you know, long form cast like yours, where you can dissect these things because it's very difficult, I think for the average person now to comb through the peer reviewed literature and know Okay, which papers are conflicted, which ones aren't. What does this all mean in layman's terms? So you guys serve a very important role. I think and distilling a lot of arcane language into, into what everyone else can understand. So, hats off to you for that. If anyone needs to wants to follow our work, you can find us on medicinal genomics. You can find me on Twitter and I have a sub stack that presents a lot more of this controversial work. And unfortunately, I made the worst possible name for my subset because no one can pronounce it, but it's dependent lactone if you ever get lost, it's the compound. That's the active ingredient in catnip. That'll lead you there.
Nick Jikomes 1:50:32
All right, Kevin McTernan Kevin mckernon. Thank you for your time.
Kevin McKernan 1:50:35
Excellent. Appreciate you
DNA & RNA Biology, mRNA Vaccines, Vax Contamination & Side Effects, Spike Protein, Ivermectin, Hop Latent Viroid | Kevin McKernan | #149