To mask or not to mask....That is the question. Part II

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  • 1DOWN4UP

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    idkfa

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    I have found it to be useless to spend time trying to correct every little thing the public says wrong in reference to my career and it usually just pizzes folks off.
    ...
    It doesn't mean they are stupid...
    It does not, indeed. Vehemently correcting someone who pretends to be an expert is important though.
     

    BugI02

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    idkfa

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    My messages here usually are a form of a PSA.
    I firmly believe that one does not need an advanced (or even university) degree to comprehend most of the topics rather well -- so long as one is willing to read, listen, and, most importantly, question the information they are being served.

    Degrees and experience help, but also provide a false sense of confidence in one's own acumen. This is otherwise known as a Dunning-Kruger effect.
    Police officers who deem themselves experts on firearms solely on the basis of their service are one such well-known example, as highlighted in many threads on this forum specifically.

    In a way, I am hesitant to engage further, because @chipbennett revealed that he simply does not possess the acumen to comprehend the literature I provided.
    He and I are, proverbially speaking, in vastly different weight categories, so it would be unfair to proceed.

    However, this might be helpful for others, and I'll try to be gentle.

    First, to get some personal jabs out of the way.
    Shot: so we're going to jump straight to ad hominem. So be it.
    This was merely a statement of fact and a response to this condescending quote, where @chipbennett clearly made assumptions about my background.:
    I've explained mRNA vaccines before. Feel free to use the search function. Absent that, Google is your friend.
    ... I'm not listening to so-called experts on the internet.

    Chaser: "Siri, show me what appeal to authority logical fallacy looks like. I know my background, education, and experience. You don't.
    So three things:
    1. I infer the answer is "no" (which is perfectly fine as indicated above).
      I see, that @chipbennett holds a BSc in Chemical Engineering and he's worked in quality control his entire career.
      Product manufacturing (including QC, GMP, and CQV) and wet lab drug development are vastly different topics, to put it mildly.
      This explains his lack of understanding of these relatively complex biological topics as well as, frankly, basic biology.

    2. Ironically, @chipbennett said
      I have direct experience with gene therapies. About a half dozen of my clients right now are CGT companies. ... This is literally what I do.
      In that post, @chipbennett did not provide any other evidence or explanations.
      This is the definition of appeal to authority.

    3. Finally, in asking if @chipbennett had any other credentials besides... whatever that is, I was actually willing to accept some form of this fallacy.
      If you will, knowing one's credentials helps understand what they are likely to know or should know.

    Second, some basic assertions.
    You are confusing the fact that mRNA can be used as part of gene therapy (a true statement) with the assertion that any use of mRNA constitutes gene therapy (a false statement), much less that the mRNA Covid vaccine is gene therapy (also a false statement).
    Yes, any use of mRNA inside the cells constitutes gene therapy, precisely because this is what mRNA fundamentally is: genetic material.
    Later, @chipbennett makes some assertions about the articles I provided, and I'll address those below.

    Your dictionary definition of "introduce", "gene", and "body" are irrelevant, and your use of them constitutes yet another logical fallacy: argumentum ad dictonarium.
    No, not every use of a dictionary constitutes a fallacy. I merely used it as a way to elaborate on part of the definition provided by the FDA and to specifically illustrate that "gene" refers to both RNA and DNA.

    Here is FDA's definition of gene therapy. To wit:

    "Gene therapy is a technique that modifies a person’s genes to treat or cure disease. Gene therapies can work by several mechanisms:
    • Replacing a disease-causing gene with a healthy copy of the gene
    • Inactivating a disease-causing gene that is not functioning properly
    • Introducing a new or modified gene into the body to help treat a disease"
    I concur; the specific part (Introducing a new or modified gene) of this definition contradicts, at least, on the surface, the umbrella definition that it modifies a person's genes.
    I've brought this up with the FDA, and I'll see what can be done about changing it.

    mRNA is nothing more than a delivery mechanism. It is what get delivered that matters.
    No, mRNA is not a delivery vehicle. mRNA is precisely what is being delivered, and it does the exact same thing in all cases: it makes protein.

    Third, onto the most important section: @chipbennett's interpretations of the scientific literature I provided as supporting evidence.
    My opinion is that he skimmed over the abstracts, misinterpreted what they said, and aligned them with his preconceived notions.

    Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis

    Intranasal vaccination for tuberculosis vaccination? In that case, the mRNA is the antigen. The only purpose it serves is to be the antigen. This is not gene therapy. This therapy does not modify the patient's genes.
    First, no, mRNA is not the primary antigen here. They specifically stress that protein production is what they were after. They mention that immune response against the mRNA itself "can be useful" in passing (and even that they call gene therapy as well).
    See for yourself:
    In HEK 293T cells transfected with mRNA-Hsp65 the protein expression was observed since the early 2 hours of the delivery of the mRNA, until 12 hours after transfection.
    ...
    We also confirmed that once the mRNA was inside the cell, the translation process could be done, with the production of Hsp65 30 minutes after the transfection process (Figure 1C). This result could explain the functionality of the vaccination, once we observed protein production and protection against M. tuberculosis infection in mice.
    ...
    In addition, the induction of specific immune response against the mRNA encoding antigen, can also be useful in gene therapy ...
    Second, this is a peer-reviewed publication, and its authors deemed it appropriate to call this gene therapy.
    This is an illustration that, at the very least, the same exact technology employed by Pfizer and Moderna is currently called gene therapy -- at the very least, here and in a large number of other publications.

    Therapeutic Prospects of mRNA-Based Gene Therapy for Glioblastoma

    mRNA-based Gene Therapy for Glioblastoma? The mRNA is the vehicle to transport synthetic RNA - the actual gene therapy - across the brain-blood barrier. The payload is the gene therapy. The mRNA is simply the delivery mechanism.
    First, this is nonsensical. mRNA is not used as a vehicle for "synthetic RNA". Here, @chipbennett likely misunderstood the following statement:
    Synthetic mRNA has emerged as an efficient gene transfection tool
    This statement means that genes encoded as mRNA are easier to deliver into the cells than genes encoded as DNA:
    To summarize, compared with pDNA delivery in gene therapy, mRNA-based gene treatment has more significant virtues...
    That's it.
    Further in the paper, the authors discuss mechanisms of mRNA delivery (again, the delivery of genes encoded as mRNA):
    • Naked mRNA Delivery
      Importantly, this is done via electroporation, which is an in vitro technique.
      Naked mRNAs can be passively transferred into cells of interest by electroporation, which is used on a certain type of cells in preclinical studies. When cells are treated with short high-field electric pulses, the difference of voltage along the cell membrane can cause temporary perforation, allowing mRNA molecules passively pass through the hole and spread into the cell.
    • Lipoplex- and Polyplex-Mediated Transfection
    • Inorganic Nanoparticle-Mediated Delivery
    • Polypeptide-Mediated Delivery
    • Virus-Mediated Delivery
    • Cell- Mediated Delivery
    • Exosome-Mediated Delivery
    This demonstrates that @chipbennett's claim that "mRNA is simply the delivery mechanism" is wrong.
    mRNA is the payload, and the delivery vehicles are listed above.

    Further, as to the BBB penetration, it is these mRNA delivery vehicles that are capable of crossing the BBB, not the mRNA itself:
    As described earlier, nano-scaled target mRNA-bearing lipoplexes, polyplexes, liposomes and exosomes are all able to cross BBB and BTB in the brain (87, 88), overcoming the natural barriers.

    Finally, again, it is the production of a protein that is the ultimate target here:
    Since Wolff et al. pioneered the concept of nucleic acid based therapy, reporting functional protein expression in target organs after the direct injection of plasmid DNA or mRNA (10), gene therapy has held a great potential ...
    ...
    It is also because of its short-term high-level expression, mRNA-based gene therapy has been intensively and almost exclusively focused on cancer treatment

    Gene therapies ... Another approach is to deliver corrected mRNA into cells ... This approach has been pioneered by Moderna Therapeutics

    mRNA-based delivery of corrected mRNA? The mRNA in this case counteracts the cell's own mRNA-based production of cell proteins, or introduces undamaged RNA to the cell cytoplasm in place of the patient's own, damaged RNA. This is gene therapy, as it is intended to modify the patient's gene expression.
    Since this is not a paper, my take on this is not going to be supported by any evidence, you can treat is as my opinion.
    No, it does not "counteract" cell's own protein production or "modify" the patient's gene expression.
    It does introduce the undamaged mRNA -- but not in place of patient's own, damaged mRNA.
    The damaged mRNA is still there, and it's still producing the damaged protein.
    The essential goal of this gene therapy is the same as it is with mRNA vaccines: to make protein. That's it.
    The function of the protein is entirely irrelevant to the definition of the technology.

    How this is different from the mRNA Covid vaccine: the mRNA payload is not gene therapy. The payload is a virus protein particle. It does not modify the patient's genes in any way. It induces the cell cytoplasm to build a protein structure. No patient genetic material is modified or impacted in any way. No patient gene expression is modified or impacted in any way.
    The mRNA is literally the payload inside the lipid nanoparticle, not the "protein particle."
    The protein is being synthesized inside patient's cells based on the genetic information in the mRNA.
    It is the same exact procedure as this gene therapy.
    Saying this is not gene therapy is the same as saying that firing a gun should be called "shooting" only if it is done during a war, but not at the range.

    Scaffold-mediated delivery for non-viral mRNA vaccines

    This is more of a medical device study related to facilitating the efficacy of mRNA therapies than a study of the mRNA therapy itself. In this case, however, the mRNA payload was DNA, so: yes, here, again, mRNA is used as part of a gene therapy.
    First, this: "mRNA payload was DNA"
    Honestly, don't let your clients see this, @chipbennett.
    Yes, this is not your field of expertise, but this is basic biology -- not to mention, given your level of seniority, you should know what you know and what you do not.

    No, you cannot have DNA as the payload in the mRNA any more than you can have a 9mm cartridge as a payload in a .50 BMG cartridge. It's physically possible, but... why?

    Again, don't take my word for it:
    In this study, we hypothesize that scaffold-mediated mRNA delivery in nanoparticle (polyplex) format is more efficient than naked RNA scaffold delivery or systemic injection of naked mRNA.
    ...
    We evaluated four types of polymer-based and lipid-based mRNA gene carriers (in vivo-jetPEI, LipofectamineTM—LF-MM, PBAE, StemfectTM—SF) as to their cytotoxicity and transfection efficiency in a range of cell lines, including DCs.
    The authors made mRNA containing Green Fluorescent Protein (GFP), mixed it with different delivery systems, and then transfected different cells in vitro as well as in mice.
    They assessed the efficacy of transfection by the levels of GFP protein expressed in those cells.
    In talking about vaccine delivery, the authors refer the reader to their earlier work (reference 32).
    In that paper, they explicitly mention "a protein or the equivalent nucleic acid vector" highlighting that it is the protein production that is the ultimate goal of gene therapy and mRNA vaccines in particular.
    With an increasing number of studies reporting enhanced innate and adaptive immune responses when antigen (as protein or the equivalent nucleic acid vector) is delivered from implanted scaffolds ...

    Finally, the conclusion of it all.
    Nope. The Agency's definition of gene therapy is dependent upon the payload, not the vector.
    Well, yeah. The genetic material that is being expressed is the payload.
    If you use genetic material in a viral or bacterial vector, the conversion of that genetic material into the protein inside the body is the goal of the entire endeavor.
    In every single instance above and in the case of mRNA COVID vaccines, the mRNA is the payload, and the vehicles usually constitute some sort of a nanocontainer.

    The Covid mRNA vaccine doesn't introduce (the payload) a gene; rather, it introduces an antigen (a protein spike, which is not genetic material) that induces an immune system response.
    It literally introduces a gene in the form of mRNA, which is translated into the spike protein.
    The function of said protein is entirely irrelevant to the definition of the technology.

    You still have no basis for asserting that anything that I have said is based merely on nothing more than my opinions and beliefs.
    I do. You provided zero evidence, managed to dramatically misinterpret every single pertinent paper I referenced, and kept regurgitating the same point over and over again without any evidence whatsoever.

    Given the assumptions you're implying here, I have little reason to care what your view of my scientific acumen is.
    Eh, it might be helpful for others.
    You are doing this community a great disservice by pretending to be an expert in the field you clearly do not understand -- and using that as sole proof for your statements.
    Just like Fauci or Walensky or Collins.
    This is the worst form of misinformation.
    Shame on you.
     

    BugI02

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    Finally, in asking if @chipbennett had any other credentials besides... whatever that is, I was actually willing to accept some form of this fallacy.
    If you will, knowing one's credentials helps understand what they are likely to know or should know.
    I feel it apropos to point out that credentialism, of which you seem to approve, is the sine qua non of appeal to authority
     

    BugI02

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    Well, yeah. The genetic material that is being expressed is the payload.
    If you use genetic material in a viral or bacterial vector, the conversion of that genetic material into the protein inside the body is the goal of the entire endeavor.
    In every single instance above and in the case of mRNA COVID vaccines, the mRNA is the payload, and the vehicles usually constitute some sort of a nanocontainer.
    Would not the goal of gene therapy be to insert regulatory material into particular chromosomes and make the change heritable in successive generations of the cell line - basically one and done? All of the gene therapy I'm aware of is targeted at inserting a good copy of a gene where the subject has a corrupt or ineffective one - which is why it is predominantly used against genetic diseases that involve one or few aberrant bits in the subject's genome
     

    chipbennett

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    Then don't trust anyone and research each claim yourself, else you'll be just as easily dissuaded by another medical professional espousing an opposite viewpoint.

    For example, @chipbennett recently replied with his "analysis" of the sources I provided on the matter of what is and what is not gene therapy, and that post is filled with astounding pseudoscientific garbage, such as "the mRNA payload was DNA" or "mRNA is the vehicle to transport synthetic RNA ... across the brain-blood barrier" (more on that in another post).

    And yet, it was delivered with such unrelenting authority, that you are convinced (based on your reply) that he is correct, and that mRNA vaccines are not gene therapies.
    It appears that you don't actually know what you're talking about (which, coincidentally, makes your Dunning-Kruger reference all the more ironic). I look forward to reading your follow-up post you mentioned.
     

    jamil

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    Then don't trust anyone and research each claim yourself, else you'll be just as easily dissuaded by another medical professional espousing an opposite viewpoint.

    For example, @chipbennett recently replied with his "analysis" of the sources I provided on the matter of what is and what is not gene therapy, and that post is filled with astounding pseudoscientific garbage, such as "the mRNA payload was DNA" or "mRNA is the vehicle to transport synthetic RNA ... across the brain-blood barrier" (more on that in another post).

    And yet, it was delivered with such unrelenting authority, that you are convinced (based on your reply) that he is correct, and that mRNA vaccines are not gene therapies.
    Don't trust anyone. You would agree that this is another way of saying "trust no one"? How far? All the way down? At some point you have to trust someone or you'll have to redo all the research that has led up to today's knowledge upon which these claims derived. Right?

    Okay, so the top level claim here is, "mRNA 'vaccines'" are really gene therapy. I don't think either of us are experts. And a little internet "research" doesn't make us experts. So at some point we both have to trust someone with more knowledge than you or me. How do I decide that I trust the source? Because they disagree with the government? Because they side with me? Because I like the answer? Because I think this answer is true?

    I think the only level at which either of us (I'm just assuming you're not a biologist because you don't talk like one :): ) can evaluate this is consistency and behavior, and all those things I mentioned elsewhere for what a non-expert can do to be reasonably assured to approximate reality.

    To me, whether it's gene therapy or not is not a hill to die on. It doesn't matter if it is or isn't. What matters is if vaccines are as safe and as effective as claimed. And in my opinion, judging from what non-expert faculties I can bring to bear, it's still undecided on that. But I have no problem at all leaving the discussion about gene therapy to people who have a working knowledge of that discipline. It doesn't matter to what I care about.
     
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    jamil

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    Because it's not an "angle" and definitions do matter.
    If not, then I have a 100 round-per-minute clip magazine to sell you.
    It's way more of an esoteric discussion than just rattling off a definition we find on the internet. There isn't a logical place in this discussion for 100 round-per minute clip magazines. No one is talking here on that level.
     

    jamil

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    Paper masks for a virus were/are a psychological crutch to keep people from panicking.
    They do nothing else.
    Yeah. I think that's kinda what it looks like to me. Why else would officials who make these policies put on the masks in the situations where they say masks should be worn, but only when they know the cameras are on, and they take them off when they think no one's watching.
     

    MCgrease08

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    A new op-ed in the Wall Street Journal highlights some of the actual numbers around kids and COVID. This was written by a doctor from John's Hopkins who was one of the first medical professionals to call for mask mandates at the start of the pandemic.


    Some of the top line highlights:

    Screenshot_20210809-132805.jpg

    Screenshot_20210809-132827.jpg

    Screenshot_20210809-132902.jpg Screenshot_20210809-132916.jpg
     

    phylodog

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    Wow he's treated 15 covid patients. What a ****ing hero..... :koolaid: This is a Dr that earns a living selling supplements to patients. At no time was I told that a Vaccine will prevent me from getting covid, but could allow me to stay out of the hospital and dying if I got it.
    How many patients has Fauci treated? Now there’s a real ****ing hero. Illegally funds research banned due to its danger level which results in an 85% manufactured pandemic and the left lines up to lick his ass as if the sun rises and sets in it.

    I suppose you’ve treated more patients? You’re not qualified to question anyone, you’ve demonstrated that here. Your opinion holds no weight, as with other trolls.
     

    jamil

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    I am beyond over the semantics and wordsmithing. For those of you that may know these words and definitions keep in mind that lay people may use these words in different context to convey information to another lay person. I have found it to be useless to spend time trying to correct every little thing the public says wrong in reference to my career and it usually just pizzes folks off.

    If not for the politicalization of this topic it wouldn't be a big deal. And if you were at the range and someone asked you to pick up, their clip they dropped and fell in your lane, you would know exactly what they meant.

    This is not the normal vaccine, the definition of which had to be changed to call it such, and lay folks lack the scientific vocabulary to precisely articulate what it is. It doesn't mean they are stupid...
    It also doesn't mean that people who call it a vaccine are trying to fool anyone. I don't care if they call it a vaccine or gene therapy. What I care about is, is it gonna cause me or my loved ones more harm than good? Is it effective? Is it worth the risk? What is the risk exactly? I don't think I have those answers to my satisfaction. That's all I need to know about these vaccines.
     

    chipbennett

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    No, I am not confusing anything, there isn't a clear delineation between the two.
    Protein therapy is, well, (primarily) therapy that uses proteins.
    Gene therapy is the therapy that employs delivering genes into the cells or altering the function of existing genes.

    But the key part of it is that goal of gene therapy is the production of protein.

    If you introduce mRNA into the body, you do so in the hope that it produces protein.
    It is not intended to do anything else.

    For example, on the topic of protein therapy vs. gene therapy, some specifically say that "Gene therapy can actually be considered a form of protein therapy."

    mRNA is not a gene. The mRNA Covid does not deliver a gene.

    Proteins are produced by ribosomes, not by mRNA. The mRNA is merely a messenger, that delivers instructions to the ribosomes. (Those instructions, by the way, are the payload - you know, what you called "pseudoscientific babble", or some such?)
     
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