The McCullough paper

A summary of an important paper on mRNA vaccine safety.

In this article, I will summarise an extensive paper on mRNA vaccine safety recently published by Dr Peter McCullough. It’s an unusual thing for a ‘layman’ to summarise a paper like McCullough’s, so why am I doing it? If I’ve learned anything throughout this pandemic, it’s that we need more participation in our own health. We’ve been cajoled into a position where life and death risk/benefit calculations are made on our behalf by an industry with an apparent lack of interest in our safety.

This was demonstrated beautifully just a few days ago when Fauci went on TV and confidently described the new bivalent vaccine he was promoting “It hasn’t been proven in a clinical trial….because we don’t have time to do a clinical trial!” There was no pushback to this absurdity. In the UK, the MHRA approved the new Pfizer vaccine based on Pfizer data from just 305 people over the age of 55. The average follow-up time was just 1.7 months. For those under 55, the safety of this new bivalent vaccine has been “extrapolated from safety data from a subset of 315 adults.” Those 315 adults didn’t actually take the bivalent vaccine, they took an Omicron-specific booster. This means the MHRA are happy for members of the public, under the age of 55, to effectively serve as trial participants for this new vaccine. From the data the MHRA provided, it appears members of the public younger than 55 will be the first people in their age bracket to take it. Are they aware of that?

As far as I’m aware, no tough questions have been asked of our health officials over this. Our ‘fourth estate’ has just absorbed the advice and broadcast it out unchallenged. Over the decades, we’ve morphed into a Science Sermon relationship where we’re given ‘The Science’ but we’re unable to credibly challenge it. To change this, we must come to understand the data that sits behind the life and death decisions being made on our behalf. We must arm ourselves with knowledge so that tough questions can be asked of the advice we are given. Maybe it’s good advice, but we ought to check.

Is the situation bad enough that we need to rush these products to market without a human clinical trial? Or should we instead pay close attention to the potential risks of these novel products? There’s excellent science being done to help inform these questions, but it’s rarely put into a format that might be more widely understood. This is my attempt to break this inertia. I believe that translating this science, as imperfect as it may be, has value. You may disagree, as is your right, you can go ahead and let me know in the open comments. As always, shares, comments and subscriptions are much appreciated.

The McCullough Paper

Dr Peter McCullough testifies at a Senate Homeland Security Committee hearing. C-Span

In June, Dr Peter McCullough and colleagues published a paper in Food and Chemical Toxicology called “Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs.” Other authors on the paper were

• Stephanie Seneff, at the Computer Science and Artificial Intelligence Laboratory, MIT.

• Greg Nigh, at Immersion Health, Portland

• Anthony M. Kyriakopoulos at Nasco AD Biotechnology Laboratory, Department of Research and Development, Piraeus, Greece

We’ll get to the paper in just one moment, but before we do, it’s worth looking at McCullough himself. McCullough is one of the most published cardiologists in American history. He’s a professor of medicine at Texas A&M, and “is recognized internationally as a leading figure in the study of chronic kidney disease as a cardiovascular risk state, having over 1,000 publications to his name and over 500 citations in the National Library of Medicine.” He’s no flake, and yet, much like any other professional who has discovered data inconvenient to the pharmaceutical industry, McCullough’s Wikipedia page says he “has promoted misinformation about COVID-19, the COVID-19 vaccine, and COVID-19 treatments.”

The first thing to note about McCullough’s ‘misinformation’ is that it is peer-reviewed and published in academic journals. His accusers, we can presume, are of the view that scientific journals and the peer review process have fallen prey to misinformation. They believe that misinformation has broken free of its nursery at Facebook and TikTok and has grown into a behemoth infecting the scientific process itself. An alternative explanation is that ‘misinformation’ is being used as a pejorative, to distract inquiry into safety issues about profitable pharmaceutical products. If your findings are inconvenient, it’s easy to tar you with the deadly ‘spreader of misinformation’ brush, no matter your credentials, even if your work is being published in the proper avenues.

This is my attempt to summarise the parts of the McCullough paper which can be reasonably understood. I’m doing this because I believe the paper has value above and beyond the immediate medical research circle it is written for.

I’ll be clear, I am not capable of critically appraising this paper, nor do I seek to. My aim is to bring its findings into a layperson format that promotes discussion, engagement, disagreement, and everything in between. Where relevant, I’ll augment the paper with information that I believe may assist in a broader understanding of its main points. One of the main values of the paper is its many references to the broad range of scientific work being done, across the world, on these new mRNA vaccines.

Some key references in the paper

• The antibodies induced by the vaccines fade in as little as 3–10 weeks after the second dose (Shrotri et al., 2021)

• Delta and now the Omicron strain are showing resistance to the antibodies induced by the vaccines, through mutations in the spike protein (Yahi et al., 2021).

• Vaccines do not prevent transmission of the disease, but can only be claimed to reduce symptom severity (Kampf, 2021a).

• A study comparing vaccination rates with COVID-19 infection rates across 68 countries and 2947 counties in the United States in early September 2021, found no correlation. Suggests that these vaccines do not protect from spread of the disease (Subramanian and Kumar, 2947)

• Mediating symptom severity is now in doubt. Outbreak in an Israeli hospital that led to the death of five fully vaccinated hospital patients (Shitrit et al., 2021).

• Brosh-Nissimov et al. (2021) reported that 22% of fully vaccinated patients hospitalised in 17 Israeli hospitals died of COVID-19.

• A recent early-release study has found that the mRNA in the COVID-19 vaccines can be detected long after the vaccine is administered. It continues to make spike glycoprotein up to sixty days post-vaccination (Röltgen et al., 2022).

• Researchers in Paris, France, revealed that patients with severe Covid-19 disease were characterized by a highly impaired type I IFN response (Hadjadj et al., 2020). McCullough paper authors argue Spike protein downregulates our IFN response.

• A paper by several researchers in the United States identified a unique and inappropriate inflammatory response in severe COVID-19 patients, characterized by low levels of both type I and type III IFNs (Blanco-Melo et al., 2020).

• In an in vitro experiment on human cells, the SARS-CoV-2 full-length spike glycoprotein was specifically shown to enter the nucleus and hinder the recruitment of the repair proteins to the site of a double-strand break “spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1” (Jiang and Mei, 2021)

• A preprint has revealed a remarkable difference between the characteristics of the immune response to an infection with SARS-CoV-2 as compared with the immune response to an mRNA vaccine against COVID-19 (Ivanova et al., 2021)

The main argument of the paper

Evidence of immune suppression by mRNA vaccines

The paper “presents evidence that vaccination induces a profound impairment in type I interferon signalling, which has diverse adverse consequences to human health.” It goes on to “identify potential profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances potentially have a causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell's palsy, liver disease, impaired adaptive immunity, impaired DNA damage response and tumorigenesis.”

To be terse, the authors think the vaccine impairs our immune system and that may have serious consequences, triggering health issues as varied as clotting to cancers.

To expand that out a bit, the mRNA vaccines use a novel gene technology (lipid nano-particles) to hijack our cell’s ability to manufacture proteins. The vaccine ‘requests’ our cells manufacture the Spike protein, which is just one small part of the full SARS-CoV-2 virus. Then our immune system stages an immune response to this apparent Spike invader, the theory being that our immune system will then recognise ‘the real’ virus when it finally arrives. At the heart of the safety issue McCullough is exploring, is the Spike protein itself, they argue that it “is neurotoxic and it impairs DNA repair mechanisms”.

The vaccine is hijacking our cell’s ability to manufacture proteins, and it is requesting they make something which is neurotoxic so that our immune system responds. This is only supposed to be temporary and localised to the site of the injection, usually the muscle tissue of your arm. This mechanism, the authors argue, risks creating a toxic quantity of Spike within the body. One of the papers McCullough cites, through experimental evidence, found that the Spike “can initiate a catastrophic immune cascade within Central Nervous System”.

This proposed cascade is complex and involves many different interactions in the body, particularly within the body’s immune system. Key to this complex interaction is the body’s “interferon signalling.” Citing a pre-print by Ivanova et al, the paper says there’s “a remarkable difference between the characteristics of the immune response to an infection with SARS-CoV-2 as compared with the immune response to an mRNA vaccine.” In observing these differences in immune response, the McCullough authors say the observations “are consistent with the idea that the anti-COVID-19 vaccines actively suppress type I IFN signalling.”

The authors believe experimental evidence shows the Spike manufactured from mRNA vaccines could suppress our body’s type I IFN signalling.

So what is IFN signalling?

According to ThermoFisher, IFN signalling “plays a critical role in the human immune response.” The signalling “triggers a complex regulatory system of innate and adaptive immune responses designed to defend against the virus.” So if the observations in this Ivanova et al paper stand up, it’s possible that the mRNA vaccines are impairing our body’s immune response by suppressing IFN signalling. This is what can trigger a ‘cascade’ of health issues.

These cascading problems are possibilities; the paper calls them ‘causal pathways’. We can’t expect that these causal pathways are triggered in everyone who has had the vaccine, but the mechanism for these problems to emerge is what the paper is trying to identify. That such pathways exist needs to be understood.

The paper cites research which shows that “Impaired type I IFN signaling is linked to many disease risks, most notably cancer, as type I IFN signaling suppresses proliferation of both viruses and cancer cells”. The many ways in which IFN signalling plays a role in our body’s ability to suppress tumours are detailed and referenced heavily in the paper, and if you’re interested in understanding that more, read section 2 entitled “Interferons”.

To grossly simplify, the McCullough paper presents evidence that IFN signalling assists in identifying tumour cells for apoptosis, the process by which your body identifies and then kills unwanted cells. Their argument is that by ‘downregulating’ our body’s IFN signalling, we risk creating a pathway for cancer, along with a proliferation of bacterial and viral infections as a result of that same impaired immune response.

But do mRNA vaccines downregulate IFN signalling?

In further demonstrating a link between the mRNA vaccine and the downregulation of IFN signalling, the authors reference this paper, published in Frontiers in Immunology in August 2021.

The paper details the mechanism by which the Spike protein from SARS-CoV-2 ‘downregulates’ IRF9 in the host. IRF9 is a part of our body’s interferon signalling and it plays a key role in our anti-viral immunity. What the paper showed, through experimentation, is that Spike, through a very complex interaction of microRNA’s (miR-148a and miR-590) interferes with USP33, a tumour suppressant pathway in your body. Speaking carefully, the authors of the paper concludes that instructing the body to manufacture Spike protein “warrants some detailed investigation regarding its impact on host immune response and other safety concerns.”

Linking these very detailed causal pathways to the mRNA vaccination itself, the McCullough paper leans heavily on this paper, and I want to point out that I can’t critically appraise it. All I can tell you is that the Mishra and Banerja paper forms a key part of the McCullough paper’s link between the mRNA vaccination and the causal pathways they identify. Much like the McCullough paper itself, it is a huge piece of work. Those interested in the complex range of interactions observed between the SARS-CoV-2 Spike and the resulting array of immune responses should read the paper in full.

Having identified the pathways by which tumour suppression might be compromised by mRNA vaccination, the McCullough paper references a case report published in Frontiers. A 66-year-old man presented with a rare form of cancer called angioimmunoblastic T cell lymphoma, a cancer of the lymphatic system. The symptoms had presented 6 months after two doses of BNT162b2 (Pfizer) mRNA vaccine. The patient was scanned to investigate the problem, and fourteen days after the scan, was given a booster dose of the same vaccine in preparation for chemotherapy. “Within a few days following the vaccine booster, the patient reported noticeable swelling of right cervical lymph nodes” which is the arm in which he had received the booster. A second scan was performed 8 days after this booster dose to get “a baseline close to the initiation of the therapy”.

Case report presented here in Frontiers.

Investigators found “a clear increase in number, size and metabolic activity of pre-existing lymphadenopathies”. They went on, “such a rapid evolution would be highly unexpected in the natural course in the disease. Since mRNA vaccination is known to induce enlargement and hypermetabolic activity of draining lymph nodes, it is reasonable to postulate that it was the trigger of the changes observed… On the longer term, the use of mRNA vaccines should clearly be avoided while other types of vaccines might be considered.”

To be clear, this was one case report. Its authors thought the case was noteworthy and worthwhile to publish. The lead author of this particular case report is Professor Michael Goldman at the Institute for Interdisciplinary Innovation in Health at the Free University of Brussels. The paper can be read in full here, and I encourage you to do that so that all the details are clear.

Commenting on the case, the McCullough paper says “lymphoid malignancies have been associated with suppression of TRAIL-R1”, which is one of the pathways they identify as being potentially downregulated, via inteferon signalling suppression, through the proliferation of Spike protein.

Too much Spike?

Having identified a pathway for suppression of IFN and the cascading effects that can cause, McCullough examines the method of action of the vaccine itself.

They describe the clever engineering that went into creating the mRNA vaccines, in which the mRNA code is wrapped in lipid nanoparticles. That innovation has created a strand of mRNA, wrapped in a tiny fatty layer, that’s able to evade the initial immune response of the body. The synthetic mRNA is able to get into the cell “through a stealth strategy that bypasses the natural immunological response to RNA-type viral infection”. But it’s this clever engineering that may be responsible for the mRNA remaining in the lymphoid “long after the vaccine is administered, and that it continues to synthesize spike gylocoprotein for up to at least sixty days post-vaccination” (Röltgen et al., 2022)

The mRNA has been detected in the body up to sixty days post-vaccination. This is a crucial point, so it’s worth reading the quote twice and consulting the study they reference if you are interested.

Why is this so important?

At the start of the vaccination campaign, regulators told us that the mRNA breaks down within a few weeks. In fact, the CDC explicitly said “Our cells break down mRNA from these vaccines and get rid of it within a few days after vaccination.” If you clicked the link and wondered why you couldn’t find that exact statement, it’s because the CDC quietly removed it from their website on July 22nd of this year. Perhaps they read the Roltgen study which McCullough cited? We can only speculate.

June 23rd, CDC remove key statement on how the mRNA vaccines work

In the EU, the advice that mRNA breaks down “shortly after vaccination” has never been removed from their website even though we now have evidence to the contrary. Not only is the mRNA detectable in the lymph nodes for up to 60 days following Pfizer vaccination, but it’s also continuing to synthesize spike protein. This could have implications for safety, because the rapid breakdown of the mRNA was part of the assumed mechanism of controlling the dose.

Fact-checkers were quick to correct people who had questions on this particular issue, they used Pfizer’s original claims to allay concerns people had over this mechanism. “The mRNA that instructs cells to create the spike protein is broken down by the cell shortly after the protein is synthesised (here)” they said, linking directly to the CDC website. There are multiple examples, dotted all over the internet, of the public being told this fact again and again.

Manufacturing Spike for “up to sixty days” is a very different proposition to your body manufacturing Spike for “a few days” as the CDC put it. Was that mechanism important? Are there safety implications for such a large difference in observed breakdown times? Rather than go public about what any of this might mean, the CDC removed the statement from their website. So a valid question for anyone able to hold the CDC to account emerges, “why was the advice that the vaccine mRNA breaks down within a few days removed from your website? If the mRNA does not break down at the speed you anticipated, are there safety implications and are those implications being actively monitored?”

Let’s hope that someone close to the CDC can demand an answer.

Another pathway to cancer and immune dysregulation

By the author’s own admission, part four of the paper is “exceedingly complicated”.

GC is the percentage of nitrogenous bases in a DNA or RNA molecule that are either guanine (G) or cytosine (C). Via GC levels, the authors identify another pathway to immune dysregulation from the mRNA vaccines. They cite a paper that shows there is “a significant enrichment of GC content in the mRNA in vaccines" measured as 53% for Pfizer, and 61% for Moderna. In the native SARS-CoV-2 mRNA, the GC level is 36%.

The important bit is that the GC levels are much higher in the synthetic mRNA contained within the vaccine than they are in the ‘natural’ SARS-CoV-2 virus. Why is this relevant?

The paper explains that the vaccine manufacturers enhance the GC content inside the synthetic mRNA because RNA with higher GC “dramatically increases the quantity of proteins produced (Mauro and Chappell, 2014).” When trying to induce an immune response to those manufactured proteins, a larger number of proteins is a design decision. This GC enrichment, a feature of the synthetic mRNA in vaccines, doesn’t come for free according to the paper’s authors. “GC enrichment content in vaccine mRNAs results in an enhanced ability for potential G-quadruplex (pG4) formations in these structures, and this could cause the onset of neurological disease (Wang et al., 2021).”

Via the same pathway, the authors identify a proliferation in cardiovascular pathology (Small and Olson, 2011), onset of neurodegeneration (Abe and Bonini, 2013), and/or cancer progression (Farazi et al., 2013).

A difference between vaccination and natural infection

The authors of the paper are keen to stress the difference in the IFN response to natural infection and vaccination. “While vaccination actively suppresses its production, natural infection promotes type I IFN production very early in the disease cycle" they say. This difference in the way our body responds to synthetic mRNA over the natural infection, and the resulting complex interactions, is what creates the conditions for these causal pathways.

A summary of the pathways

The paper provides this graphic which helps to summarise the various pathways for health problems triggered by SARS-CoV-2 mRNA vaccination. The graph helps to demonstrate the various knock-on effects of each particular pathway. Start the graphic in the middle of the left hand side at “SARS-CoV-2 mRNA vaccination”.

Looking for evidence in VAERS

Having identified key pathways by which mRNA might trigger disease through suppression of the human body’s immune response, the authors look to the pharmacosurveillance system for evidence of it happening post-vaccination.

The VAERS database is the CDC’s Vaccine Adverse Event Reporting System. If a doctor believes their patient has had an adverse reaction to the vaccine, they can report it to this database. The authors are forced to look in VAERS for evidence of their causal pathways manifesting in the public because the Phase 3 trials “were terminated early and placebo arms given the injection.” Put simply, the trials were inexplicably terminated early, meaning we no longer have a control group, and therefore don’t have trial data we can use to look for these safety signals. In a medical rollout that had been done carefully, we’d have a control group available to us to look for these long-term safety signals, but instead, authors are forced to look in the VAERS system for evidence of safety problems.

Causal links to a range of adverse events

The ‘backstory’ to all of this is a massive uptick in VAERS reports since the rollout of the Covid-19 vaccines. The uptick in reports is best understood via the graph below, taken from openvaers.com. It shows the unprecedented rise in reports between 2021 and 2022. Every year, VAERS gets reports of side effects from the 44 recommended vaccine doses that Americans are expected to have before their 18th birthday. There is no shortage of vaccines being administered which could be associated with an adverse event, and yet right after the Covid-19 vaccination program, the number of VAERS reports exploded to never before seen levels. There have been more VAERS reports since the mRNA rollout than in all the other previous years combined.

Graph taken from openvaers.com

One criticism of the VAERS data is that ‘anyone’ can submit a report, the argument being that the massive uptick of adverse reactions we’ve seen in the VAERS database is because anti-vaxx activists flood the system with nonsense reports. The McCullough paper tackles this head-on; “an interim analysis of deaths cited previously found that health service employees were the VAERS reporter in 67% of reports analyzed (Nandha and Singh, 2012)*, suggesting a large portion of VAERS reports are submitted by medical professionals and not the public.” To add to that, submitting a false report to VAERS is a “violation of federal law, punishable by fine and imprisonment”. So we can be confident that the majority of the VAERS reports are genuine.

*Note to the authors, here the citation is incorrect, it should actually point to McLachlan et al, published in 2021.

So what about the scale of the problem? On the issue of the reports themselves, “a widely cited report noted that fewer than 1% of all vaccine-related adverse events are reported to VAERS (Lazarus et al., 2010)”. That means the numbers in VAERS are much lower than the ‘real’ number of events, but determining exactly how large the under-reporting factor is is not easy. “Rose (2021) published a much more sophisticated analysis of VAERS data to offer an estimate of underreporting by a factor of 31 (Rose, 2021).” The CDC themselves admit that events reported to VAERS represent “only a small fraction of actual adverse events” (Vaers Home, 2021). Put simply, the VAERS system isn’t capturing all of the adverse events associated with the vaccine. Based on known under-reporting rates, the real number of adverse events from the mRNA vaccines is likely to be significantly higher.

So what is actually reported?

The paper says “Over the 31-year history of VAERS, up to February 3, 2022, there were a total of 10,321 deaths reported as a ‘symptom’ in association with any vaccine, and 8,241 (80%) of those deaths were linked to COVID-19 vaccines.”

It’s worth reading that twice. Keep in mind the under-reporting factor.

The paper goes on, “of COVID-19 VAERS-reported deaths as of June 2021, only 14% could have vaccination ruled out as a cause (McLachlan et al., 2021). This strongly suggests that these unprecedented vaccines exhibit unusual mechanisms of toxicity that go well beyond what is seen with more traditional vaccines… There are 27 times as many reports for COVID-19 vaccines as would be expected if its adverse reactions were comparable to those from the flu vaccine.”

But the scale of reports is not enough. Instead, the authors wanted to look in VAERS specifically for symptoms that are known to be associated with the causal pathways they identified in the paper. To recap, they presented evidence for a causal pathway between the mRNA vaccines and nerve damage, central nervous system inflammation, damage to the heart and liver, thrombosis (clotting), neurodegenerative disease and cancer. If they could find evidence of these problems happening in people via the VAERS database, “the possibility of a causal relationship is strengthened through both the causal pathways we have described in this paper, and the strong temporal association between injections and reported adverse events.”

They created a list of symptoms known to be associated with the causal pathways they argue are triggered by the vaccine. They then looked for VAERS reports which have that symptom in the “SYMPTOM” field of the report. For the reports in the year 2021, they then calculated what percentage of those reports were about the Covid-19 vaccines. For symptoms associated with inflammation or damage to the nerves, the Covid-19 vaccines represented 96% to 98% of all VAERS reports that year. For symptoms of heart and liver conditions, the Covid-19 vaccines made up 98% of all the reports, for symptoms associated with thrombosis, the Covid-19 vaccines made up 98.7% of all reports, for symptoms related to neurodegenerative disease they made up 95% of all reports, and for cancer symptoms, although smaller numbers, they made up 96% of all reports.

There’s an important caveat on cancer that I will just quote in full. “Cancer is a disease generally understood to take months or, more commonly, years to progress from an initial malignant transformation in a cell to development of a clinically recognized condition. Since VAERS reports of adverse events are happening primarily within the first month or even the first few days after vaccination (Rose, 2021), it seems likely that the acceleration of cancer progression following vaccines would be a difficult signal to recognize. Furthermore, most people do not expect cancer to be an adverse event that could be caused by a vaccine, and hence they fail to enter a report when cancer develops shortly after vaccination. However, as we have outlined in our paper, if the mRNA vaccinations are leading to widespread dysregulation of oncogene controls, cell cycle regulation, and apoptosis, then VAERS reports should reflect an increase in reports of cancer, relative to the other vaccines, even if the numbers are small.”

Conclusions

The paper summarises its three main aspects, a subversion of innate immunity via IFN signalling leading to multiple viral reactivations, the dysregulation of the body’s system for preventing genetic mutations leading to potential proliferation in cancers, and high levels of inflammation caused by the mRNA producing high levels of Spike. “Should any of these potentials be fully realized, the impact on billions of people around the world could be enormous and could contribute to both the short-term and long-term disease burden our health care system faces.”

“Billions of lives are potentially at risk, given the large number of individuals injected with the SARS-CoV-2 mRNA vaccines and the broad range of adverse outcomes we have described. We call on the public health institutions to demonstrate, with evidence, why the issues discussed in this paper are not relevant to public health, or to acknowledge that they are and to act accordingly.”

As best I can, I have tried to present to you the data inside the McCullough paper. I’m absolutely sure that medical researchers are not moved nor convinced by the data in the paper. Wherever that debate is taking place, my intention is to bring it out in the open. So my question to anyone who read this far, especially those qualified to critically appraise the work, what do you make of this paper? Are its arguments sound? Are there reasons to be more conservative with our vaccination strategy? Can we dismiss these identified causal pathways until such time that we have better evidence? Are the authors of the paper mistaken?

This is an open thread.