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To: exDemMom
So, your distrust of "Big Pharma" scientists basically means that you distrust any scientist who does research.

No, I just know better than to trust Big Pharma.

Remember FDA-approved Vioxx?

Safe and effective, until it wasn't.

Remember the $18 BILLION (yes, with a "B") fine for the false claims made while marketing Vioxx?

Guess which company made it.

Notice how that company didn't rush pell-mell into manufactured RNA jobs (specifically engineered to resist degradation by the body) masquerading as vaccines.

Troll.

73 posted on 10/26/2023 11:00:24 PM PDT by grey_whiskers ( The opinions are solely those of the author and are subject to change without notice.)
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To: grey_whiskers
The situation with Vioxx was that the effect size was too small to detect in a clinical trial population. The initial clinical trial population was 5,000 people. The risk of cardiovascular events occurring after taking Vioxx was low enough that it might not be detected in a study group this size.

The challenge for people analyzing drug safety is to determine whether the rate of cardiovascular events is higher in the population taking the study drug than it is in a matched control population. Doing this kind of analysis requires very heavy-duty statistical analysis.

Merck voluntarily initiated post-approval studies when its own post-market data suggested there might be a problem. And Merck voluntarily recalled Vioxx from the pharmacies in 2004 so that it could no longer be prescribed. The FDA did not order these actions. The FDA did request for Merck to do more studies in order to reintroduce Vioxx into the market, which Merck did not do. In October, 2021, Merck sent a letter to the FDA requesting the FDA to withdraw approval for the drug. The FDA withdrew approval for all of the previously approved forms of the drug in September, 2022.

The actual sequence of events does not suggest to me that Merck is some eeeeeevil big pharma company that pushes dangerous drugs onto the market. Instead, it shows that Merck was being responsible and took the initiative to recall the drug themselves.

The FDA went on to require all manufacturers of NSAID drugs to include labelling describing gastrointestinal and cardiovascular risks resulting from taking these drugs. In addition, the FDA now requires a black box warning to be included in the labelling of all prescription NSAIDs. Editorial note: A black box warning is the most serious kind of warning. When you are prescribed a drug with a black box warning, it is because your primary care provider has determined that the benefit of taking the drug outweighs the risk.

Instead of reading some inflammatory anti-science blog, try reading more factual articles. You can tell an article is based on facts by the lack of incendiary language and lack of blaming "Big Pharma" or "Big Government" or whatever the bogeyman of the day is. The FDA has an informative webpage on Vioxx and there is also an entry in the Federal Register about it. I also included an article published by a group called drugwatch.

Sources:

Vioxx (rofecoxib) Questions and Answers

Merck Sharp & Dohme Corp.; Withdrawal of Approval of New Drug Applications for VIOXX (Rofecoxib) Tablets and Suspension.

Vioxx

76 posted on 10/27/2023 5:23:07 AM PDT by exDemMom (Dr. exDemMom, infectious disease and vaccines research specialist.)
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To: grey_whiskers
Notice how that company didn't rush pell-mell into manufactured RNA jobs (specifically engineered to resist degradation by the body) masquerading as vaccines.

Ah, I see that you do not have a background in nucleic acid chemistry. Lucky for you, half of my PhD was based on learning all of the basics about nucleic acid chemistry. This field of science is called "molecular biology."

Now, I do not know the term "manufactured RNA jobs" and it actually does not make much sense. Are those jobs where people are employed to make RNA in a laboratory? Anyways...

The purpose of the modified RNA is to bypass the innate immune response against foreign RNA. Foreign RNA is typically the RNA contained in food or in microorganisms in your body. In addition to the innate immune response which just destroys the RNA, RNA can provoke an adaptive immune response, meaning that it provokes the formation of T-cells, B-cells, and antibodies against the RNA. Since the purpose of a vaccine is to cause an adaptive response to proteins, the adaptive immunity raised against RNA is problematic for a couple of reasons. An unmodified mRNA vaccine formulation might not survive long enough to reach the lymph nodes where the adaptive immune response takes place. And immunity against a viral mRNA is useless, since all viruses package their mRNA inside a protein-studded lipid membrane, where the immune system can't see it.

The specific modification of the RNA is to add a methyl group to the uracil, making 1-methylpseudo UTP. (UTP=uracil triphosphate) With this modification, the immune system no longer recognizes the foreign RNA. However, all of the RNA metabolism enzymes recognize it just like unmodified RNA. This means that the RNA polymerases that make the mRNA are perfectly capable of making the 1-methylpseudo UTP modified RNA. And the RNAse enzymes that chew RNA into its component nucleotides work equally well to chew up the 1-methylpseudo UTP modified RNA.

So, when you get your modified mRNA Covid-19 shot, the particles containing the mRNA enter the lymph nodes closest to the injection site. Cells in the lymph nodes internalize the particles by fusing with the lipid membrane and releasing the mRNA into the cytosol. Once there, the mRNA attaches to ribosomes where it directs the formation of modified spike protein. Since the spike protein is a membrane bound protein, it is inserted into the cell membrane so that the cell ends up having spike protein on its surface. (This also happens during viral infection.) Once the protein synthesis is complete, the ribosome releases the mRNA, which is then destroyed by RNAses inside the cell. mRNA within a cell typically has a half-life of less than a day; sometimes the half-life is just minutes, depending on the specific mRNA molecule.

Any of the following papers describing mRNA vaccine development prior to the pandemic will give you more details on the rationale of mRNA modification:

Modified mRNA Vaccines Protect against Zika Virus Infection.

Modified mRNA-Based Vaccines Elicit Robust Immune Responses and Protect Guinea Pigs From Ebola Virus Disease.

Efficient Targeting and Activation of Antigen-Presenting Cells In Vivo after Modified mRNA Vaccine Administration in Rhesus Macaques.

77 posted on 10/27/2023 6:06:32 AM PDT by exDemMom (Dr. exDemMom, infectious disease and vaccines research specialist.)
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