Limitations to the Feb 25 paper on reverse transcription notwithstanding, something has to be radically extending the half-life well beyond anything that could be predicted from the known science.
Excellent work Chris & it reminds me much of the warnings from Geneticist & RNA expert Alexandra Henrion-Caud which include reverse transcription. An experimental drug based on what appears to be limited studies & understanding of an extremely complex system, seems to beg the question - What could possibly go wrong ?
Mar 2, 2022·edited Mar 2, 2022Liked by Chris Masterjohn, PhD
Chris, this is the best breakdown of this very concerning paper. Making the links to the lymph node study is also helpful to potentially find a common mechanism between the two studies - because WHY is the mRNA still being found so long after the initial injection? The fact that we don't have a clear answer to this, and why this is contrary to all the public health assurances that it'd be gone in a jiffy, is totally unconscionable. As you highlight, it's not like the estimations were off by mere hours or something. There is literally no other comparison of it lasting this long in the body. This should have been a serious pump the brakes moment if there were proper animal trials.
I also wonder if this can be tied into the negative effectiveness the data is showing regarding the vaccines, because multiple explanations are still being put forth as to why that's happening. (Extended production of an out of date epitope perhaps via this reverse transcription, or some kind of autoimmunity induced by the exosomes?). It's frighteningly bewildering as a layman, but crucially, as you state, "these questions should have been settled with well done experiments prior to ever having conducted human trials." EXACTLY! We shouldn't have to be playing detective AFTER this has already been given to hundreds of millions of people.
Anyway, thank you for the clear analysis and I am looking forward to the next posts regarding the spike protein toxicity.
As far as the vaccine goes, Its persistence as mRNA-->ribosome protein production and lingering extracellular presence aside, the concept of cytotoxic spike proteins purposefully utilized for humeral immunity, after seeing the havoc they have wrought on the vascular systems of those infected with the virus, seems preposterous.
Just wanted to say that your articles are the best I have found on these topics. I am a layperson, but you explain so effectively that I can usually follow the gist of it.
Thank you for your thorough analysis and questioning.
We all need to do two things to move towards better and not worse.
1) Keep gently talking with friends and family. We need not be emotional or push too hard that they will run the other way, like mentioning wef or planned depopulation, in my opinion. They just need the facts and to be told the reason you say anything is because you care about them. I wrote the following post because even after a year of explaining, I was asked this question https://leemuller.substack.com/p/but-is-it-experimental
If the 50% of us in the know, is able to bring just ONE other person into the light, we will have a chance.
2) Call out the 120 Democratic and 91 Republican Representatives currently in the U.S. Congress who voted to pass the multi-billion dollar 21st Century Cures Act (2016) that enabled uninformed consent and pushed "Real World Evidence" during the past two years. Contact our officials to hold them accountable to: preserve our Constitutional rights by ending and preventing mandates, compensate and provide help to the vaccine injured, and remove liability protection enacted through the PREP Act (2005 and 2020). - RightingTheWrongs.org
Very nice. I was beginning to wonder why the conversation on the integration paper was narrowing on the chromosome / not chromosome question, since that is irrelevant (I also don't understand why the authors mention this in their own text). Chromosomes are a transient state. The question of whether any given DNA in the nucleus divides with fidelity is not litigated by whether it is included in the chromosomes during division. It's pretty safe to declare DNA part of the "genome" of a cell as soon as it is in the nucleus.
I am also glad you emailed the authors about the problems with the sequencing methods. I was going to do the same but couldn't think of a way to word it besides "did you literally just include a reverse transcriptase step for all samples without saying so?"
I think we should definitely consider the "slow drip" possibility. What if the bubbles are just not releasing the mRNA, but sitting around somewhere until "dislodged," either due to manufacturing issues or nefarious secret alternate formulations, etc.
Integration is possibly the stronger explanation. But on the other hand if I were to set expectations for the results based on the assumption of integration in advance, I would be surprised at such a high rate of detected transcribed mRNA as inferred by finding it in the germ centers. It's a very complicated issue.
Spike itself seems to be capable of forming "storage" centers in the form of breakdown-resistant micro-clots, which may be instrumental in Long Covid or Long Vaccine - https://www.theguardian.com/commentisfree/2022/jan/05/long-covid-research-microclots. Perhaps these storage centers are created by the first-secreted spike before all of the LNPs have left circulation, and some of the LNPs become entrapped in these before being taken into cells. This creates the slow-drip...? Who knows.
Very interesting points. I believe on integration that most just take as dogma that integration is what "matters" to the point where many people are totally unaware of the work showing it is not the be-all-end-all of defining the genome. In fact, those authors of last year's paper state that negative sense strands are evidence of integration. They are not, because extrachromosomal circular DNA is double-stranded as well. So they are simply evidence of successful reverse transcription.
BTW, I did a lot of work trying to develop and shore up my sequestering theory and couldn't defend it from a more obvious explanation - spike and LNPs are being preserved in the normal (but under-studied) germinal center Follicular Dendritic Cell immune-complex cycle. In case you are interested: https://unglossed.substack.com/p/the-60-day-rna-mystery-spoiler-summary
“ In the case of HIV, for example, non-integrated DNA is capable of lowering CD4 expression in T cells”
This is something I have been thinking about from the beginning. I’ve compared Covid to a retrovirus and wondered precisely which mechanism made it seem to cause autoimmune issues in some people. Needless to say, a vaccine would certainly be capable of causing a far worse autoimmune reaction or condition.
While the “written into the human genome” part isn’t 100% clear, the mRNA half-life comparisons are completely terrifying and telling on their own.
In situations like this I like to look backwards in order to look forward. So my question is, did the vaccine developers know this and lie, or did it really surprise them? I say this not to spark a conspiracy theory, but to perhaps find some more insight into the effects by defining the motive.
So, if we have spike proteins circulating for up to 4 months wouldn't we expect to see Spike antibodies staying elevated also for 4 months or longer? Why do we see S antibodies waning rapidly in the 3 to 4 months following a jab? WW
Perhaps look into polyamines, and synthetic polyamine analogs. From what I've read, polyamines function as a sort of helical structural element for mRNA and other genetic material. Synthetic versions of these (i.e. not one of the 3 iterations of "S"-named chains) have been developed. I do not know if it's officially recognized as being used in mRNA vacc. tech.
I'm looking around, and here's this for example:
Formulation and Delivery Technologies for mRNA Vaccines, June 2, 2020
Polymeric materials, including *polyamines*, dendrimers, and copolymers, are functional materials capable of delivering mRNA vaccines. Similar to functional lipid-based carriers, polymers can also protect RNA from RNase-mediated degradation [...]
Cationic polymers, such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, [...]"
PEI and PAMAM, I believe, qualify as synthetic polyamine analogs.
"...explaining the persistence of the mRNA at the 60-day timepoint at the levels shown here would require invoking an implausibly long half-life of 9-26 days."
"ALC-0315 has no known biology. In the absence of this ‘biological relevance’ the applicant used an estimation of >95% elimination of ALC-0315 to represent the essential elimination from the body. The elimination half-life of ALC-0315 in the liver following IV administration in the rat is approximately 6-8 days. These data indicate that 95% elimination of ALC-0315 will occur approx. 30-40 days following final administration in the rat.
Based on the understanding of the process involved in the terminal half-life, redistribution from tissues into which the lipid nanoparticle is delivered, a similar half-life and time to 95% elimination in human is expected (Mahmood et al, 2010). Examination of the scaling of the comparable lipids (PEG2000-C-DMG, DLin-MC3-DMA) in patisiran indicates that the half-life of these lipids appears to scale with a value approaching the typically used exponent for half-life (0.25). [b] If this is the case for ALC-0315 we may expect a half-life approximating 20-30 days in human for ALC-0315 and 4-5 months for 95% elimination of the lipid [/b] (Mahmood et al, 2010)."
From your article:
"This is 2 to 6 times the upper bound of plausibility using the longest-lasting human mRNAs, 4 to 11 times the half-life predicted by the theoretical model, and 22-108 times the half-life that would be expected of typical human mRNAs or natural coronavirus mRNAs.
Since this is semi-quantitative, cross-sectional data, we must regard any of these back-of-the-envelope calculations with a grain of salt. The point is not to try to precisely quantify the half-life, but just to get a general feel for whether it makes sense that the mRNA is hanging around this long.
It doesn’t.
Not without invoking some unforeseen mechanisms of preserving it or replicating it.
While the lipid nanoparticles were expected (page 54) to take 4-5 months to be 95% gone, [i] they should be quickly delivering their mRNA cargo to cells [/i] , otherwise the immune response would take forever to get going. Perhaps they have some slow-drip component to keep [i] delivering this cargo [/i] over the course of those 4-5 months?"
From the link, pg. 53:
"The PEG-lipid (ALC-0159) is designed to largely exchange out of the LNP after administration and before uptake into target cells, whereas the aminolipid (ALC-0315) is critical to the efficient intracellular delivery of the mRNA through endosomal uptake and release and must remain with the LNP."
Back to the article:
"This could explain why just when it threatens to bottom out at the end of the graph, it rebounds."
And lastly, from the link pg. 54:
"Both lipids showed an essentially similar PK profile in clinic with a strongly biphasic profile and long terminal half-lives."
IMO, ALC-0315 is not just delivering mRNA as cargo out from the LNP, but is also providing structure to the mRNA analagous to what polyamines do for natural mRNA. So, could it be that the aminolipid stays bound to the phosphate groups on the mRNA which makes it resistant to degradation for quite some time?
Thanks! I fixed the first one. On the second, I meant it as if it were a substance to find in some or no quantity. Like, "ice cream is only found in the trash can in 50% of households," although I see how "virus" could mean any viremia rather than viremia from SARS-CoV-2. I'm kind of happy with my grammatical choice though I could see the argument against it.
Thanks Chris - yeah I wasn't sure about the 2nd one but just wanted to point it out just in case. Anyway, I'm deleting my original comment as I previously stated. Cheers!
Yes, they would inherit the spike in the membrane. However, without a mechanism of duplicating the mRNA, eventually it would be degraded and eventually the spikes would be degraded if they are not attacked and sequestered or destroyed by the immune system first, so it would be a temporary situation.
Excellent work Chris & it reminds me much of the warnings from Geneticist & RNA expert Alexandra Henrion-Caud which include reverse transcription. An experimental drug based on what appears to be limited studies & understanding of an extremely complex system, seems to beg the question - What could possibly go wrong ?
Chris, this is the best breakdown of this very concerning paper. Making the links to the lymph node study is also helpful to potentially find a common mechanism between the two studies - because WHY is the mRNA still being found so long after the initial injection? The fact that we don't have a clear answer to this, and why this is contrary to all the public health assurances that it'd be gone in a jiffy, is totally unconscionable. As you highlight, it's not like the estimations were off by mere hours or something. There is literally no other comparison of it lasting this long in the body. This should have been a serious pump the brakes moment if there were proper animal trials.
I also wonder if this can be tied into the negative effectiveness the data is showing regarding the vaccines, because multiple explanations are still being put forth as to why that's happening. (Extended production of an out of date epitope perhaps via this reverse transcription, or some kind of autoimmunity induced by the exosomes?). It's frighteningly bewildering as a layman, but crucially, as you state, "these questions should have been settled with well done experiments prior to ever having conducted human trials." EXACTLY! We shouldn't have to be playing detective AFTER this has already been given to hundreds of millions of people.
Anyway, thank you for the clear analysis and I am looking forward to the next posts regarding the spike protein toxicity.
I will be looking forward to your discussion of spike protein toxicity. The endothelial damage, and disruption of the BBB have been fretted over since at least mid 2021, (J Biol Regul Homeost Agents, May-Jun 2021;35(3):833-838.(Editorial) and https://www.salk.edu/news-release/the-novel-coronavirus-spike-protein-plays-additional-key-role-in-illness/)
As far as the vaccine goes, Its persistence as mRNA-->ribosome protein production and lingering extracellular presence aside, the concept of cytotoxic spike proteins purposefully utilized for humeral immunity, after seeing the havoc they have wrought on the vascular systems of those infected with the virus, seems preposterous.
Sorry if this far too simplistic, but could Seneff, et al(s) data dive into the VAERS results, a thoughtful discussion into the Interferon 1 system's down regulation from spike protein exposure--with resultant disruption of viral and cancer surveillance--also pose a mechanism for persistence? (https://www.authorea.com/users/455597/articles/552937-innate-immune-suppression-by-sars-cov-2-mrna-vaccinations-the-role-of-g-quadruplexes-exosomes-and-micrornas)
Just wanted to say that your articles are the best I have found on these topics. I am a layperson, but you explain so effectively that I can usually follow the gist of it.
Thanks for the analysis. I was definitely waiting for something like this before giving any credence to the reports I had heard.
Thank you for your thorough analysis and questioning.
We all need to do two things to move towards better and not worse.
1) Keep gently talking with friends and family. We need not be emotional or push too hard that they will run the other way, like mentioning wef or planned depopulation, in my opinion. They just need the facts and to be told the reason you say anything is because you care about them. I wrote the following post because even after a year of explaining, I was asked this question https://leemuller.substack.com/p/but-is-it-experimental
If the 50% of us in the know, is able to bring just ONE other person into the light, we will have a chance.
2) Call out the 120 Democratic and 91 Republican Representatives currently in the U.S. Congress who voted to pass the multi-billion dollar 21st Century Cures Act (2016) that enabled uninformed consent and pushed "Real World Evidence" during the past two years. Contact our officials to hold them accountable to: preserve our Constitutional rights by ending and preventing mandates, compensate and provide help to the vaccine injured, and remove liability protection enacted through the PREP Act (2005 and 2020). - RightingTheWrongs.org
Thank you so much for your analysis and explanation. I really enjoy reading your topics.
Very nice. I was beginning to wonder why the conversation on the integration paper was narrowing on the chromosome / not chromosome question, since that is irrelevant (I also don't understand why the authors mention this in their own text). Chromosomes are a transient state. The question of whether any given DNA in the nucleus divides with fidelity is not litigated by whether it is included in the chromosomes during division. It's pretty safe to declare DNA part of the "genome" of a cell as soon as it is in the nucleus.
I am also glad you emailed the authors about the problems with the sequencing methods. I was going to do the same but couldn't think of a way to word it besides "did you literally just include a reverse transcriptase step for all samples without saying so?"
I think we should definitely consider the "slow drip" possibility. What if the bubbles are just not releasing the mRNA, but sitting around somewhere until "dislodged," either due to manufacturing issues or nefarious secret alternate formulations, etc.
Integration is possibly the stronger explanation. But on the other hand if I were to set expectations for the results based on the assumption of integration in advance, I would be surprised at such a high rate of detected transcribed mRNA as inferred by finding it in the germ centers. It's a very complicated issue.
Spike itself seems to be capable of forming "storage" centers in the form of breakdown-resistant micro-clots, which may be instrumental in Long Covid or Long Vaccine - https://www.theguardian.com/commentisfree/2022/jan/05/long-covid-research-microclots. Perhaps these storage centers are created by the first-secreted spike before all of the LNPs have left circulation, and some of the LNPs become entrapped in these before being taken into cells. This creates the slow-drip...? Who knows.
Very interesting points. I believe on integration that most just take as dogma that integration is what "matters" to the point where many people are totally unaware of the work showing it is not the be-all-end-all of defining the genome. In fact, those authors of last year's paper state that negative sense strands are evidence of integration. They are not, because extrachromosomal circular DNA is double-stranded as well. So they are simply evidence of successful reverse transcription.
BTW, I did a lot of work trying to develop and shore up my sequestering theory and couldn't defend it from a more obvious explanation - spike and LNPs are being preserved in the normal (but under-studied) germinal center Follicular Dendritic Cell immune-complex cycle. In case you are interested: https://unglossed.substack.com/p/the-60-day-rna-mystery-spoiler-summary
Another excellent dive into this paper Chris thank you so much
“ In the case of HIV, for example, non-integrated DNA is capable of lowering CD4 expression in T cells”
This is something I have been thinking about from the beginning. I’ve compared Covid to a retrovirus and wondered precisely which mechanism made it seem to cause autoimmune issues in some people. Needless to say, a vaccine would certainly be capable of causing a far worse autoimmune reaction or condition.
While the “written into the human genome” part isn’t 100% clear, the mRNA half-life comparisons are completely terrifying and telling on their own.
In situations like this I like to look backwards in order to look forward. So my question is, did the vaccine developers know this and lie, or did it really surprise them? I say this not to spark a conspiracy theory, but to perhaps find some more insight into the effects by defining the motive.
Hey Chris, this study is making the rounds again recently. Did the study authors ever respond to your questions/concerns?
No, they did not.
Good to know, thanks
So, if we have spike proteins circulating for up to 4 months wouldn't we expect to see Spike antibodies staying elevated also for 4 months or longer? Why do we see S antibodies waning rapidly in the 3 to 4 months following a jab? WW
The exosome paper found that the persistence of antibodies was correlated with the spike protein on exosomes.
Hello,
Perhaps look into polyamines, and synthetic polyamine analogs. From what I've read, polyamines function as a sort of helical structural element for mRNA and other genetic material. Synthetic versions of these (i.e. not one of the 3 iterations of "S"-named chains) have been developed. I do not know if it's officially recognized as being used in mRNA vacc. tech.
I'm looking around, and here's this for example:
Formulation and Delivery Technologies for mRNA Vaccines, June 2, 2020
https://link.springer.com/chapter/10.1007/82_2020_217
"3.1.2 Polymer-based Delivery
Polymeric materials, including *polyamines*, dendrimers, and copolymers, are functional materials capable of delivering mRNA vaccines. Similar to functional lipid-based carriers, polymers can also protect RNA from RNase-mediated degradation [...]
Cationic polymers, such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, [...]"
PEI and PAMAM, I believe, qualify as synthetic polyamine analogs.
Thank you
From your article:
"...explaining the persistence of the mRNA at the 60-day timepoint at the levels shown here would require invoking an implausibly long half-life of 9-26 days."
From https://www.ema.europa.eu/en/documents/assessment-report/comirnaty-epar-public-assessment-report_en.pdf , pg. 53-54:
"ALC-0315 has no known biology. In the absence of this ‘biological relevance’ the applicant used an estimation of >95% elimination of ALC-0315 to represent the essential elimination from the body. The elimination half-life of ALC-0315 in the liver following IV administration in the rat is approximately 6-8 days. These data indicate that 95% elimination of ALC-0315 will occur approx. 30-40 days following final administration in the rat.
Based on the understanding of the process involved in the terminal half-life, redistribution from tissues into which the lipid nanoparticle is delivered, a similar half-life and time to 95% elimination in human is expected (Mahmood et al, 2010). Examination of the scaling of the comparable lipids (PEG2000-C-DMG, DLin-MC3-DMA) in patisiran indicates that the half-life of these lipids appears to scale with a value approaching the typically used exponent for half-life (0.25). [b] If this is the case for ALC-0315 we may expect a half-life approximating 20-30 days in human for ALC-0315 and 4-5 months for 95% elimination of the lipid [/b] (Mahmood et al, 2010)."
From your article:
"This is 2 to 6 times the upper bound of plausibility using the longest-lasting human mRNAs, 4 to 11 times the half-life predicted by the theoretical model, and 22-108 times the half-life that would be expected of typical human mRNAs or natural coronavirus mRNAs.
Since this is semi-quantitative, cross-sectional data, we must regard any of these back-of-the-envelope calculations with a grain of salt. The point is not to try to precisely quantify the half-life, but just to get a general feel for whether it makes sense that the mRNA is hanging around this long.
It doesn’t.
Not without invoking some unforeseen mechanisms of preserving it or replicating it.
While the lipid nanoparticles were expected (page 54) to take 4-5 months to be 95% gone, [i] they should be quickly delivering their mRNA cargo to cells [/i] , otherwise the immune response would take forever to get going. Perhaps they have some slow-drip component to keep [i] delivering this cargo [/i] over the course of those 4-5 months?"
From the link, pg. 53:
"The PEG-lipid (ALC-0159) is designed to largely exchange out of the LNP after administration and before uptake into target cells, whereas the aminolipid (ALC-0315) is critical to the efficient intracellular delivery of the mRNA through endosomal uptake and release and must remain with the LNP."
Back to the article:
"This could explain why just when it threatens to bottom out at the end of the graph, it rebounds."
And lastly, from the link pg. 54:
"Both lipids showed an essentially similar PK profile in clinic with a strongly biphasic profile and long terminal half-lives."
IMO, ALC-0315 is not just delivering mRNA as cargo out from the LNP, but is also providing structure to the mRNA analagous to what polyamines do for natural mRNA. So, could it be that the aminolipid stays bound to the phosphate groups on the mRNA which makes it resistant to degradation for quite some time?
see:
Polyamines: Regulation and Molecular Functions
http://www.weizmann.ac.il/molgen/Kahana/polyamines
for an overview on the topic.
Has anyone found anything interesting in the Pfizer documents at phmpt.org?
Thanks! I fixed the first one. On the second, I meant it as if it were a substance to find in some or no quantity. Like, "ice cream is only found in the trash can in 50% of households," although I see how "virus" could mean any viremia rather than viremia from SARS-CoV-2. I'm kind of happy with my grammatical choice though I could see the argument against it.
Thanks Chris - yeah I wasn't sure about the 2nd one but just wanted to point it out just in case. Anyway, I'm deleting my original comment as I previously stated. Cheers!
Yes, they would inherit the spike in the membrane. However, without a mechanism of duplicating the mRNA, eventually it would be degraded and eventually the spikes would be degraded if they are not attacked and sequestered or destroyed by the immune system first, so it would be a temporary situation.