COVID-19 vaccines are incompletely tested gene therapies: end of

How fact-checkers deceive us and medicines regulators cut corners

Dive right into this post:

• Prologue

• The speech on gene therapy by Bayer AG Pharmaceuticals’ president: a slip of the tongue?

• Reuters: sugar coating and incompetence, or intent?

• Health Education England: mainly incompetence, or intent?

• Fact-check this!

• A twitter fight

• The European definition of gene therapy, with a twist

• The Federal Food and Drug Administration: COVID-19 vaccines are gene therapy

• Epilogue: What does it all mean?

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Prologue

In my previous post I shared a video of Stefan Olerich, president of Bayer AG Pharmaceuticals, giving a speech at the World Health Summit in October 2021. In the video he states that “ultimately the [COVID-19] mRNA vaccines are an example for that cell and gene therapy” (and that should include also viral vector DNA vaccines). I thought that the video would highlight in a simple and direct way the true nature of these COVID-19 vaccines.

But, since then, I found that fact-checkers have not failed to jump at the video. They aim at defending the notion that COVID-19 vaccines do not use gene therapy technologies [for the rest of the post I will just use ‘gene therapy’]. Their pieces on this topic are gems of either disinformation or misinformation (as defined, for instance, in the proposed UK Online Safety Bill). Are their authors, or their sponsors, misleading us?

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Definitions of disinformation, misinformation, malinformation, and information (DMMI) as given in the draft of the UK Online Safety Bill.

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Note: Pfizer-BioNTech and Moderna injections are mRNA vaccines. AstraZeneca and Johnson and Johnson injections are viral vector DNA vaccines. In the rest of the post I will refer to them as COVID-19 vaccines.

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I felt compelled to fact-check the fact-checkers, and show that COVID-19 vaccines are indeed counted in the class of gene therapies, with all their implications. I also take the opportunity to show that European and US medicine regulators understand the true nature of these novel vaccines, but cut corners in their approval process.

I note here that a ‘therapy’ is somehing to treat a disease, rather than preventing it. As a result, semantically, vaccines cannot be considered therapies. But, as you will see in what follows, ‘gene therapy’ is indeed used in the literature as an umbrella term for any product that uses a genetic technology, including vaccines.

The speech on gene therapy by Bayer AG Pharmaceuticals’ president: a slip of the tongue?

In one remarkable fact-checking piece published in June, the Public Health Comunications Collaborative (PHCC) – a US CDC Foundation sponsored fact-check site aimed at public health officials – states that Mr Oelrich “misspoke when he referred to the Covid-19 vaccine as an example of these gene therapies.”

For one thing, he seems pretty confident of his statement. He is so sure about it that, after his supposed blunder, he goes on to say:

“I have always liked to say if we had surveyed two years ago in the public “would you have been willing to take a gene or cell therapy and inject it into your body”, we would have probably had a 95% refusal rate. I think this pandemic has also opened many people’s eyes to innovation in a way that was maybe not possible before.“

If you ask me, the reference to the public now being primed to accept a gene therapy after having accepted en masse the Covid-19 pandemic vaccines, indicates that the two technologies are one and the same.

It is bizarre, though, that the PHCC also refers to a fact-checking article in Italian, from a Facebook affiliate site, which takes a different angle to debunk what Mr Oelrich said.

The Italian debunker – who is a phenomenal example of paternalistic and pompous “journalism” – points out that Oelrich exact words were “example for that cell and gene therapy” and not “example of that cell and gene therapy”. This is correct. The article explains that with “example for” instead of “example of” Mr Oelrich meant that the Covid-19 vaccines should set an example for the future of gene therapy innovation. This level of pedantry is prize worthy.

We should not trust this Italian as a lecturer on English grammar in a sentence uttered by a native German speaker. In any case, we should not resolve this issue on grammar, semantic, or form.

In fact, the Italian piece in the end contradicts itself by accepting Bayer’s version that Mr Oelrich indeed misspoke. They allegedly asked Bayer, and the spokesperson’s answer was:

“It was an obvious slip of the tongue. According to Bayer, mRNA is not a gene therapy in the sense of general understanding [emphasis is mine].”

Bayer feels the need to qualify the “not a gene therapy” with a vague “in the sense of general understanding”: suspicious.

Reuters: sugar coating and incompetence, or intent?

Reuters surpasses the splendid specimens of disinformation quoted above with a post also published in June. In addition to the argument put forward in the Italian post, Reuters reports statements by the “expert” virologist Dr Adam Taylor, research fellow at the Menzies Health Institute, Queensland, Griffith University. He is reported there as having stated that:

“Gene therapy, in the classical sense, involves making deliberate changes to a patient’s DNA in order to treat or cure them. mRNA vaccines will not enter a cell’s nucleus that houses your DNA genome. There is zero risk of these vaccines integrating into our own genome or altering our genetic makeup.”

Again, there is a reference to gene therapy with a vague qualification “in the classical sense”. More suspicion. Dr Taylor has to do that to sugar coat the problem. He disinforms or misinforms us by not saying that what he calls gene therapy “in the classical sense” – and what Bayer calls gene therapy “in the sense of general understanding” – is gene editing, a subset of gene therapy. A medicine does not have to integrate into our genome to be defined as gene therapy. I will show you the evidence further below.

Dr Taylor also states that “mRNA vaccines will not enter a cell’s nucleus”. This statement seems to be used with the intent of reassuring us that the injected genetic code will not be too close to our DNA, which is in the nucleus. Pity that he did not mention that the other class of COVID-19 vaccines, viral vector DNA, do enter the nucleus. Gavi, the Vaccine Alliance itself tell us that:

“Once injected into the body, these vaccine viruses begin infecting our cells and inserting their genetic material – including the antigen gene [the spike protein DNA]– into the cells’ nuclei.“

Are we then supposed to worry about the possible modification of our DNA by AstraZeneca and Johnson & Johnson vaccines?

Dr Taylor concludes by telling us that “there is zero risk of these [mRNA] vaccines integrating into our genome”. This is false. There are three potential sources of integration of external (called ‘exogenous.) mRNA into the cell DNA:

• retroviruses that might be present already in the cell

• retroviral infections, for example, HIV

• L1-mediated retroposition

Not zero mechanisms, but three different mechanisms. A fascinating but worrying review of these mechanisms in the context of COVID-19 vaccines is given in a paper appeared in the journal Genes in April (a little too late).

After all, molecular biology is not an exact science, and several cellular mechanism are only partially understood. Stating that something in biology has zero chances of happening might be a statement that will not age well.

Or, let’s take it from the horse’s mouth. BioNTech itself has not excluded for their mRNA vaccine the possibility of mRNA integration into cells’ DNA. In their Form 20-F filed at the US Securities and Exchange Commission in March 2020, they state that:

“mRNA is highly unlikely to localize to the nucleus, integrate into cell DNA, or otherwise make any permanent changes to cell DNA.” (p.26)

(Thank you @a_nineties for sharing with me on Twitter the link to Form 20-F.)

A cursory exploration of the literature suggests that nobody knows how high the unlikelihood of integration events is.

Health Education England: mainly incompetence, or intent?

Worse yet, Reuters post above links to a Health Education England (HEE) fact-check piece. It comes under its ‘Genomic Education Programme’, which:

“exists to deliver and advise on learning and development opportunities that prepare current and future NHS professionals to make the best use of genomics in their practice.“

A suggestion to my fellow healthcare professionals: stay away from it.

Again, we can see the common narrative. First it says there that:

“The mRNA from the vaccines does not enter the cell nucleus or interact with the DNA at all, so it does not constitute gene therapy.”

Here they have used Reuters’ bold and reassuring statements: no chances that the mRNA enters the nucleus, or interacts with our DNA. Because of that, mRNA vaccines are not gene therapy. More sugar coating.

Also, it gives the impression that to be considered gene therapy the nucleus has to be involved.

Second, what is appalling of this masterpiece of fact-checking post is how it describes the AstraZeneca COVID-19 vaccine:

“The Oxford-AstraZeneca vaccine is a type of vaccine called a viral vector. It works by using a harmless virus that has been altered to have the SARS-CoV-2 [spike] protein on its surface.”

Who has written this piece? (I have kept a printout, in case they take it down.) The AstraZeneca vaccine consists of an inactive adenovirus modified to transport a DNA molecule encoding the spike protein. The virus does not have the spike protein on its surface, but it carries the instruction for our cells to produce it. The virus and its DNA package do enter our cells’ nucleus. There the DNA is processed by our cells, in parallel with our own DNA.

HEE instead tells us that the vaccine has the spike protein around its transport virus. This might lead the reader of the post to assume that no DNA goes into our cells’ nucleus: misinformation or disinformation?

I am not done yet. The next one is priceless.

HEE has a glossary of terms. Its ‘gene therapy’ states:

“Gene therapy delivers a functioning copy of a gene to cells. This is usually done using a non-infectious virus to deliver the gene to the target cells. It does not integrate the new DNA into the chromosomes [emphasis is mine] but exists as free-floating DNA in the nucleus where it can be transcribed into mRNA. Once transcribed, the mRNA is processed in the same way as mRNA transcribed from chromosomal DNA.“

First, this is a narrow definition of gene therapy, as it excludes gene editing. Second, they have just described AstraZeneca and Johnson & Johnson COVID-19 vaccines! Then, they are gene therapy. HEE has fact-checked itself.

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The restrictive definition of gene therapy as given by Health Education England Genomic Education Programme website. Their description reflects the working of the AstraZeneca and Johnson & Johnson viral vector DNA vaccine. You could not make it up.

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I pray that no healthcare professional has learned about COVID-19 vaccines from this collection of junk.

Fact check this!

During my web searches for my research on this post, it did not take me long to find the website of the American Society of Gene & Cell Therapy. The society’s aim is to foster genetic and cellular therapies. It has a section dedicated to patients education. The section looks more like a bait for prospective participants in gene therapy clinical trials. In any case, below is a screenshot of a page of the website with its navigation menu. Do you note anything familiar?

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The education website of the American Society of Gene & Cell Therapy. They showcase an entire section on COVID-19 mRNA and viral vector DNA vaccines (the latter referred to in the websites as adenovirus-based vaccines).

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Quick! Someone tell the ASGCT that the pharmaceutical industry has moved on since the emergency approval of COVID-19 vaccines, and they are not gene therapy anymore.

Another snippet of evidence from the vast literature on gene therapy is from a review article from the journal Applied Biosafety. Its three authors are employees of Advarra, a clinical research consultancy company. The article has the rampant title: “A Changing World in Gene Therapy Research: Exciting Opportunities for Medical Advancement and Biosafety Challenges”. A drug pusher piece.

In a table in the article showcasing all the US “Food and Drug Administration-approved products containing recombinant or synthetic nucleic acid molecules” we find what is shown below.

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Extract from a table in the review article “A Changing World in Gene Therapy Research: Exciting Opportunities for Medical Advancement and Biosafety Challenges”. The table lists all products containing recombinant or synthetic nucleic acid molecules approved by the FDA. COVID-19 mRNA and viral vector DNA vaccines sit proudly within it [note: AstraZeneca is not there because it is not approved in the US.]

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In the text of the article, commenting on the table, the authors write:

“When the products are categorized by disease indication, we can gauge the level of progress gene therapy has made in each type of disease. [..] Six FDA approvals have been issued for infectious disease vaccines, although four of them are emergency use authorizations for vaccines against SARS-CoV-2 intended to quell the COVID-19 pandemic.”

For the fact-checkers, nothing to see here. All in all, it’s just another slip of the tongue.

A twitter fight

I admit it: I got involved in a Twitter fight (but I kept my cool) with a user self-described as ex-biochemist. He was adamant to convince me that COVID-19 vaccines are not gene therapies. To that end, he posted a link to an article from Nature, the “God” of science journals. There it says:

“Today, because of that progress, many gene therapies employ adeno-associated virus (AAV) or retrovirus vectors, each with their own pros and cons, in addition to improved versions of the adenovirus vector from the earliest trials. The genetic cargo delivered by most AAV vectors remains within the cell as separate, free-floating elements rather than stably integrating into the host cell’s genome.“

Again, integration in the host genome is not required for a drug to be considered a gene therapy. Also, apart from the fact that AstraZeneca and Johnson & Johnson vaccines use an adenovirus and not an adeno-associated virus, the above quote is a description of how these vaccines work.

As expiation for my sin, I have been told I have to share my Twitter fight exchange. Here is an extract from it.

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Part of my Twitter fight exchange over the ‘COVID-19 as gene therapies‘ argument. I am not proud of it. But I still think the car metaphor is spot on!

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The argument of @allangmiller1 is one that other detractors on Twitter use. They used the semantic argument: vaccines are designed to prevent COVID-19, not to correct a genetic disease. As a result, they are different from gene therapy. Wrong. Medicine regulators include prophylactic, that is, preventative medicinal products like vaccines in the definition of gene therapy, as I show in the next section.

I have to tell you, dear reader, that my car metaphor that I used in my Twitter response above landed on infertile soil. I rewrite it here for you, but I change it to make it perhaps more effective:

A COVID-19 vaccine is like the car in my family. I use it to go to the superstore, while my partner uses it to go to the workplace.

In the metaphor, the car is the gene therapy machinery. My partner and I are the genetic payload. The superstore and the workplace are the protein expressed by the genetic payload, that is, the end result.

We end up in different places, but we are both using the same vehicle. You can call it a shopping vehicle or a work vehicle, but it is the same vehicle. Similarly, whether you are using a gene therapy, that is, an mRNA or viral vector DNA machinery, as a vaccine or as a cure for a genetic disease, the machinery stays the same. With all its possible harms.

That is why it is important that a gene therapy is tested for safety regardless of the end product of the therapy, like MOT safety requirements for my car are the same, regardless of where I drive with it.

The European definition of gene therapy, with a twist

You will never see a fact-checker referring to the 180-page directive of the European Parliament (Directive 2001/83/EC, Annex I, part IV, section 2.1). In there is the definition of gene therapy. Despite Brexit, the UK Medicines and Healthcare products Regulatory Agency (MHRA) has decided that this directive will continue to apply in the UK, too. The directive defines a gene therapy medicinal product (GTMP) as:

“A biological medicinal product which has the following characteristics:

(a) it contains an active substance which contains or consists of a recombinant nucleic acid [that is, mRNA or DNA] used in or administered to human beings with a view to regulating, repairing, adding or deleting a genetic sequence;

(b) its therapeutic, prophylactic [emphasis is mine] or diagnostic effect relates directly to the recombinant nucleic acid sequence it contains, or to the product of genetic expression of this sequence.”

Note that both conditions (a) and (b) needs to be met. By their design, mRNA and vector-DNA COVID-19 vaccines meet the conditions:

(a) They contain a recombinant nucleic acid (mRNA or DNA); the nucleic acid adds to (and does not have to integrate with) the genetic sequence of the cells in the vaccine recipient’s body;

(b) They provide a prophylaxis (that is, prevention) effect on COVID-19 disease by inducing production of the spike protein (the product of genetic expression).

But, with a stroke of genius, the directive immediately states that:

“Gene therapy medicinal products shall not include vaccines against infectious diseases.”

So, you see. By fiat, all those vaccines that in all effects use gene therapy modalities, should be classified as vaccines and not as gene therapies.

An European Medicines Agency (EMA) own guideline document, is not embarrassed to admit that, for example, a viral vector DNA product:

“could fulfil [sic] the definition of Gene Therapy Medicinal Products (GTMP) when administered for example in oncology, but similar products would not be classified GTMPs when intended as prophylactic against infectious disease [that is, as vaccine; emphasis is mine].”

In other words, same machinery, with a differentiation based on intended use. That is my car metaphor.

Why did the European Parliament bothered with this caveat?

Well, the answer to this question is the whole motivation to a post about proving that COVID-19 vaccines are gene therapy. The European Parliament caveat gives the pharmaceutical industry one of those shortcuts that the regulators worldwide have told us they have never allowed.

The regulators have done a big favour to pharmaceutical companies and their shareholders. The motivation of the caveat is that the regulatory approval requirements for testing a vaccine are much less strict than for drug classified as gene therapies. This means that, for vaccines based on mRNA and viral vector DNA gene therapies, pharmaceutical companies can bypass stricter scrutiny upon application for approval.

For example, one key requirement for gene therapies approval is for the manufacturer to provide detailed studies of pharmacokinetics – what the human body does to the drug, that is, how the body absorbs, distributes, metabolises and eliminates the drug. I say that even for novel COVID-19 gene therapy vaccines it is important to have complete understanding about where in the human body the vaccines components go and for how long they stay there. Regulators think otherwise. The drug companies were not required to provide those studies. And so they did not.

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My “artistic rendering” of an extract from the MHRA approval document for the AstraZeneca viral vector DNA COVID-19 vaccine. There is no requirement to provide pharmacokinetics studies. Nothing to see here, literally.

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The Federal Food and Drug Administration: COVID-19 vaccines are gene therapy

To check what the Food and Drug Administration (FDA) says about gene therapy it only takes to look at ‘Section VIII - Definitions’ of “Long Term Follow-Up After Administration of Human Gene Therapy Products - Guidance for Industry“.

“Human gene therapy product: FDA generally considers human gene therapy products to include all products that mediate their effects by transcription or translation of transferred genetic material or [emphasis is mine] by specifically altering host (human) genetic sequences.”

Here alteration of host genetic sequence is an optional feature of gene therapy. As a result, according to the FDA, all mRNA and viral vector DNA COVID-19 vaccines are gene therapies.

How do the fact-checkers solve this problem? Reuters, for example, avoids linking to the official definition above. It links instead to a FDA lay-person description webpage about gene therapy. There it says:

“Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1.

Gene therapy is a technique that modifies a person’s genes to treat or cure disease.”

Again, here it gives the impression that gene therapy is only gene editing used to treat or cure a disease, and not to prevent a disease like COVID-19.

But, did you notice the timid “1” in the text above? It is the link to the official document containing the complete definition of gene therapy. Rather than giving us in this page the whole definition of gene therapy, the FDA hid it behind a tiny link. FDA and fact-checkers deceiving us by omission.

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FDA webpage intended to give the “lay person” a definition of gene therapy. The definition in this page is restrictive, as it implies gene editing. The tiny “1” is the link to the full definition in the official FDA documents. There, the definition includes gene therapy as applied to COVID-19 vaccines.

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Even BionNTech knew back in March 2020 what Mr Oelrich knew and Bayer AG spokesperson did not seem to know. In the same Form 20-F we read:

“[…] In the United States, and in the European Union, mRNA therapies have been classified as gene therapy medicinal products” (p.14)

Thank you BioNTech for your honesty towards, at least, the US Securities and Exchange Commission.

Epilogue: What does it all mean?

Knowing that COVID-19 vaccines are gene therapy vaccines, and that they have been considered to be only vaccines, has several serious implications. Two of them are pivotal. One is in respect to possible vaccine harms. The other is in respect to the relationship between healthcare professionals and their patients.

First, regulators have allowed pharmaceutical companies to take shortcuts in the approval process of COVID-19 vaccines. In this post I only hinted at the lack of pharmacokinetics studies, but other human study requirements were bypassed. One example is toxicology study, carcinogenicity in particular.

Second, a gross misrepresentation of the product offered to the worldwide population has undermined a true informed consent. It seems now clear that the majority of healthcare professionals had a poor understanding of the nature of these vaccines. I have showed how the official source for genomic education of English healthcare professionals, HEE, makes serious blunders in the description of COVID-19 vaccines and gene therapy.

By all means, I have not exhausted all arguments on the vaccines versus gene therapy debate, or on their potential mechanisms for harms. But Substack editor is warning me that “Post is too long for email”!

Finally, there are several more fact-checking pieces out there that have attempted to “debunk” Mr Oelrich’s speech or the gene therapy “conspiracy theory”. There is no need to give them any consideration. They all follow the common narrative dictated by those with vested interests. They are all, well… clones.