Muta­tion risk for the human genome: Pfizer mRNA, & Parkinson’s disease through spike prions?

Wikimedia: genome gradient

By MATTHIAS OHLDORF | There are strong efforts on the part of the phar­maceu­tical industry (Moderna) to switch the entire vaccine produc­tion to RNA tech­no­logy, as it can gene­rate astro­no­mical profits. Curr­ently, there is a de facto field trial with Sars-Cov‑2 mRNA vaccines by Pfizer BioN­Tech and Moderna on millions of people. This makes it all the more important to look at what long-term conse­quences this new tech­no­logy method can probably have for the human genome, the next genera­tions and thus for the human species.

To explain this ques­tion in more detail, we first need to take a closer look at the func­tional basics of this novel mRNA vaccine technology.

How do the Pfizer and Moderna vaccines work?

Both vaccines (Moderna, Pfizer) are based on mRNA that codes for the so-called spike protein, an enve­lope protein of Sars-Cov‑2. The first two doses are admi­nis­tered 3–4 weeks apart, into the (arm) muscle. Booster vaccines are to be admi­nis­tered annu­ally. Both vaccines are deep-frozen, Pfizer at ‑70°C, Moderna at – 20°C, to protect the sensi­tive single-stranded mRNA from enzy­matic digestion.

In contrast, the vaccines of the compe­ting products from Astra­ze­neca and Johnson & Johnson are based on so-called double-stranded vector DNA. The vector, i.e. the trans­port container into the cell, is in this case a cold or cold virus (adeno­virus) that has been gene­ti­cally modi­fied so that it is unable to repro­duce inde­pendently in the cell. The vectors of both vaccines are grown on tumou­rised embryonic stem cells. For Astra­ze­neca these are embryonic kidney cells (HEK-293) and for Johnson & Johnson these are foetal retinal cells. Apart from ethical ques­tions, the cell lines are based on aborted foetuses, the ques­tion of conta­mi­na­tion with human DNA is a safety risk, espe­cially since tumour genes can also enter the human orga­nism in this way.

To be protected from enzymes, the strands of the mRNA vaccines are surrounded by an arti­fi­cial fat or lipid shell. These are lipid nano­par­ti­cles (LNP). In addi­tion, the mRNAs are stabi­lised by modi­fied nucleo­tides. In this specific case, instead of the natu­rally occur­ring nucleo­tide uridine, this is a variant of uridine that is specially charac­te­rised by a so-called methyla­tion: methyl uridine. The mRNA vaccines deliver the spike protein to antigen-presen­ting cells, acti­vating the immune system [link]. Are the two vaccines really as mature as the manu­fac­tu­rers claim?

Speed first: vaccine deve­lo­p­ment and approval

In the USA and Europe, poli­ti­cians and autho­ri­ties thought they had to push the pace on behalf of the phar­maceu­tical industry: Pfizer’s vaccine was approved for the Euro­pean market under the brand name Comirnaty by the Euro­pean Medi­cines Agency (EMA) on 22 December 2020 after a proces­sing period of only three weeks. A few days earlier, this had been done by the FDA for the US market [link]. In the US, the produc­tion and distri­bu­tion was raised by the manu­fac­tu­rers toge­ther with the Defence and Health Depart­ments under the name „Opera­tion Warp Speed“. Proudly, Pfizer announced in a release:

„Today’s condi­tional marke­ting autho­ri­sa­tion by the Euro­pean Commis­sion is a historic achie­ve­ment. It is the first vaccine to be tested and approved in less than a year in a large-scale study in more than 44,000 subjects. This great achie­ve­ment is based on decades of work by many scien­tists around the world and is also a confir­ma­tion of our successful colla­bo­ra­tion with our partner Pfizer,“ said Ugur Sahin, M.D., CEO and co-founder of BioN­Tech. „As a company founded and head­quar­tered in the heart of Europe, we are parti­cu­larly excited to make our vaccine avail­able to the Euro­pean popu­la­tion in the coming days. We will be collec­ting further effi­cacy and safety data in our study parti­ci­pants over the next two years, as well as evalua­ting the vaccine against any emer­ging mutations.“

Pfizer, 22 December 2020 [link]

The same pattern is repeated with the so far wisely omitted approval for infants between 6 months and 5 years: Pfizer received emer­gency approval for the US market on 17 June [link]. It is only a matter of time before this also happens in the EU. How do appro­vals normally work and what chances do the diffe­rent vaccine cate­go­ries have of getting into pati­ents‘ bodies at all?

Vaccine deve­lo­p­ment: simple, complex and unprecedented

According to a study funded by the Bill & Melinda Gates Foun­da­tion [link], there are three cate­go­ries of vaccines in the approval process: simple, complex and unpre­ce­dented. The following illus­tra­tion provides an over­view: The first two cate­go­ries are stan­dard (simple) or modi­fied (complex) vaccines produced with estab­lished tech­no­lo­gies. Unpre­ce­dented vaccines are those newly deve­loped against dise­ases for which there has never been a vaccine before, such as HIV or malaria.

Young et al. 2018

Both complex and unpre­ce­dented vaccines are extre­mely costly to approve, with each phase costing around US$250 million and taking an average of 12.5 years. More import­antly, the unpre­ce­dented vaccine trials have only a 5% chance of even success­fully comple­ting Phase II, and even if they clear that hurdle, only a 40% chance of success­fully comple­ting Phase III and getting marke­ting approval. So there is a „low proba­bi­lity of success, espe­cially for unpre­ce­dented vaccines“ [link].

In addi­tion to the extre­mely acce­le­rated deve­lo­p­ment time (!) and successful comple­tion of Phase III, two vaccines were also approved almost simul­ta­ne­ously, the one from Moderna [Link] and the one from Pfizer [Link]! In addi­tion, the vaccines from Astra­ze­neca and Johnson & Johnson, which are based on other mecha­nisms, also received emer­gency appro­vals after a short deve­lo­p­ment period. In view of the above proba­bi­li­ties, coin­ci­dences can be ruled out here; it is probably a matter of mafia-corrup­tive processes. The claimed drug effi­cacy of 90–95 % (Pfizer) or 94.1 % (Moderna) was called into ques­tion early on [Link].

Were fore­see­able conse­quences ignored due to poli­tical pres­sure during the approval process? Is there a danger that the human genome and the genetic mate­rial of future genera­tions will be perma­nently damaged?

Perma­nent changes in the human genome

The clas­sical linear model of protein biosyn­thesis, which postu­lates a one-way street from DNA to mRNA and finally protein trans­la­tion, has been outdated for decades.

Wiki­media: ADN_planeta_tierra

The enzyme reverse tran­scrip­tase, which converts mRNA into DNA, has been known for a long time; initi­ally it was only known from retro­vi­ruses, to which Sars-Cov‑2 also belongs. For some time now, the enzyme has also been known from so-called mobile DNA elements in the human genome. These make up about 1/3 of the genome! They consist of two elements that belong to the retro­tran­so­sons, so-called SINE’s and LINE’s (short and long inco­po­rated nuclear elements). They used to be regarded as func­tion­less „junk DNA“, a view that has since been revised. LINEs convert RNA into DNA using reverse tran­scrip­tase, they incor­po­rate RNA from external sources (e.g. retro­vi­ruses) into the genome. SINEs rear­range this DNA in the genome, espe­cially in adeno­sine-thymine rich regions. This results in some­times exten­sive genetic changes in the genome.

In addi­tion, the human genome has endo­ge­nous retro­vi­ruses (HERVs) that closely resemble retro­vi­ruses and retro­trans­po­sons. A promi­nent example of such a sequence is the protein syncytin. It allows the ferti­lised egg (embryo) to implant in the uterine wall and bears a strong resem­blance to the spike protein of Sars-Cov‑2! There are (contro­ver­sial) specu­la­tions that the acti­va­tion of the immune system by the spike proteins (as a side effect?) attacks the homo­lo­gous syncytin and thus makes implan­ta­tion of the embryo impos­sible and thus leads to infer­ti­lity [Link]. There are also exoge­nous, i.e. infec­tious and inde­pen­dent retro­vi­ruses, which can, however, inte­grate into the genome.

Confirmed in the lab

Is this a purely academic possi­bi­lity? Defi­ni­tely not! A rese­arch group has already confirmed the possi­bi­lity of inte­gra­ting spike mRNA into the human genome, albeit initi­ally only in cell cultures. The rese­arch group came up with this expe­ri­mental arran­ge­ment because they noticed that vacci­nated pati­ents repeatedly suffered from Sars-Cov‑2 outbreaks [Link]. The long-term conse­quences of the inte­gra­tion of mRNA into the genome for genetic health cannot be esti­mated at all! Parti­cu­larly dange­rous: LINE‑1 is also active in the gametes, i.e. sperm and egg cells, and thus theo­re­ti­cally enables the incor­po­ra­tion and trans­mis­sion of foreign RNA to the next genera­tion [Link]. According to a Swedish study [Link], spike protein inter­feres with the cell’s own DNA repair mecha­nisms, thus addi­tio­nally leading to more genome mutations.

What long-term side effects can vacci­nated people possibly expect after many years?

Wrongly „folded“ proteins: Alzheimer’s and Parkinson’s disease

A poten­tial danger for the nervous system comes from the (possibly) infec­tious spike proteins. Such dise­ases often only appear after many years or decades. The func­tio­n­ally most important compo­nent of both vaccines are Sars-Cov2 spike protein-enco­ding mRNA mole­cules, the proteins resul­ting from protein biosyn­thesis can form so-called prions. Prions cause dege­ne­ra­tive changes in nerve tissue. Known dise­ases that can be traced back to them are Parkinson’s and Alzheimer’s dise­ases. Prions are protein mole­cules that do not exist in their „normal“ three-dimen­sional form (confor­ma­tion) but are misfolded. They spread by also trig­ge­ring patho­lo­gical, i.e. disease-causing, struc­tural changes in neigh­bou­ring proteins.

Wiki­media: 776px-Alzheimers_Disease

Over time, prions form fibre bundles and plaques in the nerve tissue. The disease pattern is illus­trated by BSE or mad cow disease: the dise­ased animals, usually sheep or cattle, were fed animal meal from conspe­ci­fics suffe­ring from similar dise­ases dama­ging the nervous system (TSE and trotter). The ingestion of infec­tious proteins via the feed (meat-and-bone meal from nerve tissue) trig­gered the above-described trans­for­ma­tion of proteins into prions in the brain. A compa­rable disease, kuru, caused by ritual canni­ba­lism (ancestor worship) of tribes in Papua New Guinea, also existed in humans until the 20th century.

Spike proteins are trans­mem­brane proteins that protrude through the lipid membranes of cells and have the small amino acid glycine incor­po­rated at both their ends (intracel­lular and extracel­lular). This so-called amino acid motif has a high poten­tial to fold over and form so-called ß‑sheets, the prion motif. It is abbre­viated GxxxG, where „G“ stands for the amino acid glycine and „x“ for any other amino acid. The arti­fi­cially produced spike mRNAs, however, have not only one such GxxxG motif, but five! This is a special feature of Sars-Cov‑2 that does not occur in other coro­na­vi­ruses. There is there­fore a high proba­bi­lity that prions are formed, with all conceivable patho­lo­gical conse­quences for the vacci­nated! In addi­tion, the vaccine mRNAs have two built-in changes (amino acid proline), which indi­rectly also increase the poten­tial for prion forma­tion. Do the mRNA vaccines or the spike proteins produced actually trigger Parkinson’s and Alzheimer’s or compa­rable dise­ases? Clinical evidence is (still) lacking, but this is very possible [link, link].

We have described a small selec­tion of the theo­re­ti­cally expected side effects and explana­tions for the mecha­nisms behind them and tried to present their occur­rence in a gene­rally compre­hen­sible way. There are many more poten­tial and clini­cally mani­fest dise­ases that could be trig­gered by diffe­rent compon­ents of the two mRNA vaccines from Moderna and Pfizer [link].

 

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