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No evidence that coronavirus genetic sequences were fabricated, contrary to preprint by Li-Meng Yan and colleagues – Health Feedback

CLAIM

Fabricated genetic sequences were used to support the hypothesis that the virus arose naturally

DETAILS

Inadequate support: The preprint by Yan et al. offers no evidence to support their claim that the genetic sequences of other coronavirus strains were fabricated to support the hypothesis that SARS-CoV-2 arose naturally.Incorrect: The fact that multiple coronavirus strains share highly similar or identical genetic or protein sequences is not evidence that those viruses were fabricated. Shared genetic or protein sequences is common among viruses that belong to the same family and indicates their evolutionary relatedness.

KEY TAKE AWAY

There is no evidence supporting the claim by Yan et al. that genetic sequences of several coronaviruses were fabricated to support the hypothesis that SARS-CoV-2 arose naturally. The presence of highly similar or identical gene and protein sequences are common among organisms that are evolutionarily related to each other. Therefore, it is expected that members of the coronavirus family share similar or identical genetic or protein features. Scientific evidence supports the hypothesis that the virus arose naturally in wildlife before it crossed over to humans.

REVIEW Uncertainty surrounding the origin of the novel coronavirus has provided fertile ground for breeding conspiracy theories, some of which Health Feedback previously found to be inaccurate and unsubstantiated (see here and here). The recent claim by virologist Li-Meng Yan that the SARS-CoV-2 virus is manmade is the latest in a long series of conspiracy theories stretching back to the beginning of the coronavirus pandemic.

On 14 September 2020, Yan and her colleagues published a preprint on the online repository Zenodo claiming that the SARS-CoV-2 virus is a product of genetic engineering. A preprint is a research paper that has not been peer-reviewed by other scientists yet. Experts who examined the preprint found it was highly flawed and provided no supporting evidence for their claims, as detailed in this Health Feedback review.

Yan et al. published a second preprint on 8 October 2020 claiming that the virus is an unrestricted bioweapon and alleging that the genetic sequences of ten other coronaviruses are fabricated and do not exist in nature. Contrary to this claim, these ten coronaviruses, including RaTG13which is the closest known relative to SARS-CoV-2 and has about 96% genome sequence identity to SARS-CoV-2[1]and some pangolin coronaviruses, were analyzed by other scientists and found to support the natural origin hypothesis for SARS-CoV-2[2-7]. The second preprint from Yan et al. received more than 130,000 views on Zenodo since it was published, and was promoted by outlets known for publishing misinformation, such as Zero Hedge and National Pulse.

The alleged motivation for fabricating genetic sequences is related to one of the primary claims by Yan et al., specifically that the bat coronaviruses ZC45 and ZXC21 provided the genetic backbone for SARS-CoV-2. In support of this claim, Yan et al. point to the 100% identity in the envelope (E) protein sequence that exists between these three viruses. The E protein is a small protein on the surface of the membrane that encloses the viral genome and is important for producing virus particles that can efficiently infect cells[8].

Firstly, the claim that the bat coronaviruses ZC45 and ZXC21 provided the genetic backbone to artificially create SARS-CoV-2 was presented in the first preprint by Yan et al. This claim was debunked by scientists, who pointed out that the genetic sequences of ZC45 and ZXC21 are very different to that of SARS-CoV-2. In fact, the virus ZC45 is only 89% related to SARS-CoV-2, said Stanley Perlman, a professor at the University of Iowa who studies coronaviruses, in this FactCheck.org article:

Perlman said it would be nearly impossible to make the reverse genetics system needed to manipulate the virus and changing its sequence to arrive at SARS-CoV-2 would be virtually impossible since it would not be known how to manipulate the virus.

Kristian Andersen, a professor at Scripps Research who studies the evolution of viruses including SARS-CoV-2, also pointed out the incongruency of the claim on Twitter: This simply cant be true there are more than 3,500 nucleotide differences between SARS-CoV-2 and these viruses.

Marvin Reitz, a virologist at the University of Maryland, put it more bluntly in his review of the first preprint: [I]t still would require more than 3,000 nucleotide substitutions [for ZC45] to become SARS-CoV-2. This is not even slightly credible; it beggars reason.

A response by scientists at the Johns Hopkins University Center for Health Security also provides a detailed rebuttal of the claims made by Yan et al. in their first preprint. It also highlights the implausible use of ZC45 and ZXC21 as the genetic backbone for SARS-CoV-2.

In short, ZC45 and ZXC21 are very different from SARS-CoV-2 in terms of genome identity. Altering a backbone from either of the two to transform it into the genome of SARS-CoV-2 would require a feat of genetic engineering that is extremely difficult, if not impossible, to accomplish with current technology.

Based on their spurious initial assumption that ZC45 and ZXC21 provided the genetic backbone for SARS-CoV-2, Yan et al. claim that the genetic sequences of RaTG13 and the other coronaviruses were fabricated to obscure the link between SARS-CoV-2 and ZC45/ZXC21, and that RaTG13 and the other coronaviruses do not exist. To support this claim, they point to the observation that all these viruses also have an E protein sequence that is 100% identical to that of ZC45 and ZXC21.

The argument by Yan et al. that the genetic sequences of some coronaviruses were fabricated to support the hypothesis that SARS-CoV-2 arose naturally does not hold up to scrutiny. In a Business Insider interview, Emma Hodcroft, a postdoctoral fellow at the University of Basel and co-developer of the Nextstrain project that studies the evolution of pathogens, including SARS-CoV-2, pointed out that most of the samples that Yans group says are fake predate the start of the pandemic. Hodcroft also explained:

This accusation implies there were years of coordination and fake sequence generation, Hodcroft said, adding: This is an incredible claim, and would require a significant evidence burden to back it up, which is missing from the paper.

Virologists have also analyzed the genome sequence of RaTG13 and found it to be authentic and supported by good-quality data.

Although some coronaviruses share certain identical genetic sequences with SARS-CoV-2, this is not evidence that the other coronaviruses were fabricated. Instead, similar or identical genetic and protein sequences of coronaviruses are evidence of their evolutionary relatedness, which is expected since these viruses all belong to the coronavirus family. Specifically, the E protein sequence of SARS-CoV-2, RaTG13, and the other coronaviruses analyzed in the preprint by Yan et al. are indeed identical to that of ZC45 and ZXC21, but this in itself does not indicate that the RaTG13 and the other coronaviruses were fabricated to mimic the E protein sequence of ZC45 and ZXC21.

Lastly, one feature of concern in both preprints by Yan and her co-authors is the listing of their affiliations as the Rule of Law Society and the Rule of Law Foundation. These two organizations have no prior experience in conducting biological research and are linked to Stephen Bannon and Wengui Guo, both of whom have published COVID-19 misinformation in the past.

Overall, the claims in the second preprint by Yan and her colleagues are as ill-founded as the claims made in their first preprint. Evidence supporting claims that the virus was engineered is lacking. In contrast, scientific analyses support the hypothesis that SARS-CoV-2 arose naturally in wildlife before crossing over to humans during a zoonotic infection (transmission of pathogens from animals/insects to humans). There are numerous examples of emerging zoonotic pathogens causing disease outbreaks throughout human history and across the world[9].

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No evidence that coronavirus genetic sequences were fabricated, contrary to preprint by Li-Meng Yan and colleagues - Health Feedback

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Genetic modification is ready to serve humanity The Miscellany News – Miscellany News

On Oct. 7, 2020, Dr. Emmanuelle Charpentier and Dr. Jennifer A. Doudna were awarded the Nobel Prize in Chemistry for their work in the field of gene editing. On top of breaking barriers as the first two women jointly awarded the chemistry prize, Charpentier and Doudnas recognition is a huge step forward for the controversial field of genetic engineering.

Humans have been practicing a form of genetic engineering ever since we started cultivating plants and livestock. Grafting two plants together dates back centuries in both the East and the West, and selective breeding was a staple technique used by even the earliest farmers. These techniques arent using advanced technology to target and change certain genes, but nevertheless the point of these exercises was to eliminate or diminish unwanted characteristics and promote the characteristics that the farmer found most useful. Wild cabbage was bred to create broccoli, brussel sprouts and domesticated cabbage. Cattle were bred to increase their edible volume. This was all uncontroversial, but it was all gene editing.

Today the techniques have changed, but the underlying mission has stayed the same: improve quality of life. Public opinion has shifted, however. Currently, more than half of adults in the U.S. believe that using genetically modified organisms (GMOs) as a food source is worse for your health than using non-modified foods. Of those, 88 percent believe that GMO foods will lead to health problems for the general populace. There is no such thing as non-modified food, but there is a stigma against food modified in a lab.

Part of this bias may be due to the way direct modification was introduced in the 1950s. In order to increase variation in plants so that selective breeding could be done more efficiently, scientists bombarded plants with radiation. This process, known as mutation breeding, was part of an effort to discover a peaceful use for the nuclear knowledge that was proliferating in the aftermath of World War II. Radiation was poorly understood by the general public in the mid-20th century. The possibilities of mutation due to radiation caused imagination to run rampant over reality: 1954s Them! stars giant insects caused by nuclear testing in the area.

The 1957 film Beginning of the End has grasshoppers eat mutated plants and then grow to enormous sizes. Even some of the most famous pop culture characters that exist today were formulated along these lines. In 1961 the Fantastic Four were given their powers by cosmic radiation. Spider-Man has had eight movies over the last 20 years, and he was famously bitten by a radioactive spider. These examples dont insinuate that people really believed that radiation could produce superheroes and skyscraper-sized insects, but they do reflect a general fear of the unknown that the gene modification of radiation could produce.

Radiation is no longer the bugaboo of the modern day, but fear of radiation has been displaced by fear of targeted gene editing, like the Crispr-Cas9 technique pioneered by Charpentier and Doudna. Some of this fear may be well founded: Theres no definite way to know that a gene edited plant or animal wont act similar to an invasive species. Presumably freed from some ailment or deficit that was limiting its growth, it is possible that a plant may grow at a pace that is higher than wanted by its creators. Nature is a delicate balance, and intervening must be done in a reasonable way that weighs the potential costs and benefits.

Mosquito reduction or elimination may not seem to be a worthwhile risk for something with unknown side effects, but that initial intuition would be wrong. Malaria, a disease transmitted mainly through mosquito bites, kills around 400,000 people per year. Zika and West Nile virus, while less deadly, are also transmitted into the human populace via mosquito. No other creature kills humans at the rate of mosquitoes. Despite the environmental damage that may be wreaked by the adjustment of the other flora and fauna to a lack of mosquitoes, gene editing to reduce mosquito population is a clear path to saving hundreds of thousands of lives every year.

With this sort of benefit in mind, the United States Environmental Protection Agency and Florida state government recently came to an agreement that will release over 750 million genetically modified mosquitoes into Florida. This is no small action and could potentially disrupt the entire food web of Florida, and possibly beyond.

The plan in Florida is to introduce a strain of Aedes Aegypti mosquitoes, a spreader of the Zika virus, that are genetically engineered so that their female offspring die off. Mosquitoes bite to extract human blood, and in this exchange mosquitoes can transfer any diseases they are carrying. Mosquitoes only bite so that they can extract iron and proteins in human blood and transfer it to the fertilized eggs that will be the next generation of that mosquitos bloodline. As such, the only mosquitoes that bite, and thus have the chance to transfer diseases, are adult females. The firm Oxitec produced a modified mosquito whose female offspring cant grow out of the larval stage. No adult females means no blood sucking, which means no disease transmission and no new mosquito larvae being produced.

A similar plan was executed in Brazil, where the Aedes Aegypti mosquito population was cut by 89 to 96 percent. With such a large reduction in mosquito population, the benefits move beyond that of just public health. Thousands of tracts of land would become more usable and see an increase in value if mosquitoes died out. Even day-to-day activities like gardening or talking walks could become much more pleasant in the absence of mosquitoes.

2020 has already shown the effects of disease and failures of public health. COVID-19 has killed over a million people; over the last 10 years, malaria has killed over four million. We have to live with COVID-19 for the foreseeable future, but gene editing has given us a tool to end malaria. Genetically modified mosquitoes should not end in Florida or with Aedes Aegypti: they should be of all species, placed all over the globe. For months the world has lived under a new biological terror. Its time we release a new biological salvation.

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5 Questions for Catherine Zabinski, author of Amber Waves: The Extraordinary Biography of Wheat, from Wild Grass to World Megacrop – UChicago News

Its harvest season! What better time to dip into agricultural history? Wheat was one of the first domesticated food crops, and for roughly 8,000 years it has been a dietary staple in Europe, West Asia, and North Africa. Today, wheat is grown on more land area than any other commercial crop, and it continues to be the most important food grain for humans. A plant this prolific surely deserves its own biography. In Amber Waves, Catherine Zabinski invites us to follow the evolutionary journey of wheat while exploring its symbiotic relationship with humans. We are introduced to the habits and history of this member of the grass family, how it lives, how it thrives, and how it arrived at its current form. We learn how our ancestors discovered and exploited the grain, which went on to be foundational to the development of civilizationfrom the wild grasses first cultivated in the Fertile Crescent to the ancient empires that sought to control its production. And in modern times, we discover wheats role in the Green Revolution and contemporary efforts to produce a perennial form. From the origins of agriculture to gluten sensitivities and genetic engineering, Amber Waves sheds new light on how we grow the food that sustains so much human life. We sent Zabinski a few questions recently to learn more about her motivations for writing the book.

How did you wind up in your field, and what do you love about it?

I am a plant and soil ecologist, and my research is on ways that soil biota and plant roots interact to increase plants ability to grow on disturbed sites. Initially, I focused my work on metal-contaminated sites, sites that have high concentrations of invasive species, and high elevation sites impacted by recreation. I was particularly interested in how disturbance affected ecological processes in soil, and how ecological restoration could address that. I started thinking about agricultural systems about ten years ago, after a sabbatical year working in France. Experiencing the importance for French people of place and how that relates to the quality of food and wine helped me to see that the questions that I ask about plant and soil interactions in natural areas and disturbed areas were equally relevant to our agricultural systems.

InAmber Waves, you explicitly set out to write a biography of wheat. Why that approach?

Scientists use a technical vocabulary for our research. Its an important aspect of advancing our knowledge, because it allows us to communicate really precisely. But that same language can serve as a barrier to talking about our work to people who arent practicing scientists. When I started thinking about expanding my audience from the students in my classes at the university to a broader public, I thought a lot about how I could write about the science underlying agriculture in a way that would be accessible and interesting. My story needed a character, and because plants are often underappreciated, I thought framing the question as a biography of one of our food plants could be a way for me and for my readers to consider our relationship to food plants from a different perspective.

While you were working on this project, what did you learn that surprised you the most?

Perhaps what surprised me the most was how much I learned. It wasnt incredibly insightful on my part, but I hadnt anticipated how much history would be involved when writing about a plant from the origins of agriculture through present day. My initial book outline pretty much jumped from early agriculture to Darwin, but the story didnt allow me to do that. Fortunately, there are historians who have done a really nice job researching food and agriculture, enabling me to pick up the threads of the story.

But there was also a big learning curve on the other end of the story, about genome sequencing and the acronym-laden vocabulary of plant genomics. I started attending genomics conferences, at first, sitting in the back and googling all the acronyms so I could understand the research being presented. Even as a scientist, the technical vocabulary can be a barrier.

Where will your research and writing take you next?

There is really no end in sight to the questions that exist about how plants and soil microbes

interact to affect plant communities and soil processes like nutrient cycling and decomposition. My lab research will continue in both natural and agricultural systems. Wes Jackson made the salient point that ecologists cant afford to ignore agricultural systems, as our need for food and for lands to grow food will only increase in coming decades.

As far as my writing, there are so many interesting stories about food, how we grow and produce that food, how placeincluding climate, soils, and local practicesaffect our food supply. Im deeply engaged in learning more about that and as Eula Biss describes it, translating those stories for people.

Whats the best book youve read lately?

Ive been enjoying Bill Bufords Dirt: Adventures in Lyon as a Chef in Training, Father, and Sleuth Looking for the Secret of French Cooking. Because much of my writing is technical science writing, I read beautifully written non-science books as a way to experience language and stories. Valeria Luisellis The Story of My Teethis an amazing homage to storytelling. Carolyn Forchs recent poetry collection, In the Lateness of the World, has been my companion lately. And I just started reading A. S. Barwichs Smellosophy: What the Nose Tells the Mind, which I anticipate will be on my favorite books list.

Catherine Zabinski is professor of plant and soil ecology in the Department of Land Resources and Environmental Sciences at Montana State University in Bozeman. She received a fellowship from the Arthur P. Sloan Foundation to work on this book.

Amber Waves is available now! Find it onour website or at your favorite bookseller.

Tags: agriculture, megacrop, wheat

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Was the MERS virus a model for the creation of COVID-19? – WION

First reported in 2012 in Saudi Arabia, Middle East Respiratory Syndrome (MERS) is a respiratory illness caused by a coronavirus with symptoms similar to the COVID-19 coronavirus, namely, fever, cough and shortness of breath with a range from none, to mild, to severe.

As of January 2020, about 2,500 cases of MERS have been reported worldwide. Human-to-human transmission typically requires close contact with an infected person, the spread being uncommon outside of hospitals.

In contrast to COVID-19, the death rate from MERS is about 35%.

MERS is believed to have originated in bats, was transmitted to camels as an intermediate host, then infecting humans, who had contact with the infected animals.

Although the COVID-19 virus has structural similarities to bat coronaviruses, its precise origin has yet to be identified.

The most distinguishing and unique structural feature of the COVID-19 virus is the furin polybasic cleavage site, a sequence of amino acids that interacts with human cell enzymes, which cut or cleave parts of the viral structure, thus contributing to the life cycle of the virus.

In the case of COVID-19, that sequence of amino acids is usually identified as proline-arginine-arginine-alanine or, in scientific notation, PRRA, which precedes an arginine-serine cleavage point, R-S.

It is unknown from where the PRRA sequence originated because it does not exist in any of the bat coronaviruses identified as close relatives of the COVID-19 virus.

A model for such a structure, however, does exist in the MERS coronavirus, which has a proline-arginine-serine-valine or PRSV sequence preceding the R-S cleavage point and having the following alignment:

COVID-19 PRRAR-S

MERS PRSVR-S

Both sequences begin with proline (P), both are polybasic having more than one arginine (R) and both have a non-polar amino acid in the fourth position, alanine (A) and valine (V), respectively, prior to the cleavage point, R-S.

It is important to note that COVID-19 and MERS are from two completely different families of coronaviruses, so one could not have evolved from the other.

According to the scientific article Structures and dynamics of the novel S1/S2 protease cleavage site loop of the SARS-CoV-2 spike glycoprotein," the presence of proline (P) is highly unusual.

Unlike other amino acids, proline produces structural rigidity in proteins and is found in only 5 out of 132 identified furin cleavage site sequences.

Likewise, alanine (A) located just prior to the R-S cleavage point exists in only 5 out of 132 furin cleavage site sequences.

In an early June scientific article, A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein, the authors claimed to have identified a bat coronavirus, called RmYN02, that appears to have a precursor of the COVID-19 furin polybasic cleavage site.

RmYN02 has a proline-alanine-alanine (PAA) insertion roughly in a similar position to the COVID-19 virus, but PAA is chemically neutral, lacks any basic amino acids and has no R-S point to be cleaved.

RmYN02's PAA sequence, therefore, cannot be considered a precursor of the COVID-19 furin polybasic cleavage site.

So, the question remains, if no yet identified close relative of COVID-19 has a similar furin polybasic cleavage site, from where did such a unique structural feature with amino acids in unusual positions arise?

Furin polybasic cleavage sites are known to increase viral infectivity and pathogenicity. Genetic engineering techniques for inserting such cleavage sites have existed for at least fifteen years.

At present, no natural evolutionary pathway has been identified to explain the presence of COVID-19s furin polybasic cleavage site.

Those who may have manufactured the COVID-19 virus, could have been trying to mimic the cleavage site found in MERS.

Furthermore, the high rate of human-to-human transmission found for COVID-19, may have resulted from "pre-adapting" the virus for human infection by serial infection or passaging of the virus using animal models genetically-engineered to express the human coronavirus receptor.

There is now a preponderance of evidence that the COVID-19 virus was the product of laboratory experimentation rather than a natural infectious "jump" from bats to humans.

China still has a lot of explaining to do.

(Lawrence Sellin, Ph.D. is a retired U.S. Army Reserve colonel, who previously worked at the U.S. Army Medical Research Institute of Infectious Diseases and conducted basic and clinical research in the pharmaceutical industry. His email address is lawrence.sellin@gmail.com)

(Disclaimer: The opinions expressed above are the personal views of the author and do not reflect the views of ZMCL.)

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A breakthrough on the horizon: Humans could begin receiving transplanted pig hearts by 2021 – Cardiovascular Business

In addition, the team added, researchers have developed new drugs that suppress the immune systems of transplant recipients when the organ comes from a different species. Before this crucial step, researchers would attempt to transplant, say, a pig heart into a baboonbut the heart would ultimately be rejected.

One of the biggest questions surrounding cardiac xenotransplantation with pigs and humans, of course, is patient safety. Could such a process lead to humans being infected with infectious diseases, for example?

That looks quite unlikely, lead author Richard N. Pierson III, MD, division of cardiac surgery at MGH and a professor at Harvard Medical School, said in a prepared statement.

The culmination of a lot of research and hard work by our group and others over the last 35 years is that it now looks as though pig-to-human heart transplantation is feasible, he added.

Pierson thinks the first humans could receive pig hearts by the end of 2021. The teams full analysis is available here.

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Dont tell me the COVID-19 virus could not have been manufactured by China – WION

So far, the global scientific community has been unable to identify a natural origin of, or a logical evolutionary pathway for, the COVID-19 virus.

In contrast, the entire history of coronavirus research is punctuated by the ubiquitous use of genetic engineering to produce new viral combinations, which makes a laboratory origin a far more likely scenario.

In 2008, just five years after the first 2002-2003 severe acute respiratory syndrome (SARS) pandemic, Dr. Ralph Baric of the University of North Carolina published an article entitled Synthetic recombinant bat SARS-like coronavirus is infectious in cultured cells and in mice, in which he described the creation in the laboratory of an entirely new virus capable of producing a human SARS-like infection:

Here, we report the design, synthesis, and recovery of the largest synthetic replicating life form, a 29.7-kb bat severe acute respiratory syndrome (SARS)-like coronavirus (Bat-SCoV), a likely progenitor to the SARS-CoV epidemic.

In that study, Baric demonstrated that his new synthetic virus was capable of infecting human lung cells to a similar extent as the first human SARS pandemic virus because he had genetically spliced the receptor binding domain (RBD) from the SARS virus onto his new artificial virus.

It is important to note that Dr Baric has been a long-time research collaborator with Zheng-Li Shi, the bat woman from the Wuhan Institute of Virology.

Similar to the 2008 study described above, Baric and Zheng-Li Shi jointly published a 2015 scientific article describing the insertion of the RBD from a newly isolated coronavirus (SHC014) into SARS-CoV-1, the coronavirus responsible for the 2002-2003 pandemic.

Baric and Zheng-Li Shi combined the components of two coronaviruses and produced another novel virus, SHC014-MA15, which showed robust viral replication both in vitro [cell cultures] and in vivo [animals], using models adapted to test for human infectivity.

Other genetic engineering techniques, such as the insertion of a furin polybasic basic cleavage site, which is found in the COVID-19 virus and in no other close natural relative, as well as individual artificial point mutations, have been widely used in coronavirus research.

Since the initial 2002-2003 SARS pandemic, which also originated in China, there have been attempts to create a broad-spectrum vaccine that would provide long-lasting protection against a variety of coronaviruses that might emerge from nature and infect humans.

One such approach has been the development of live-attenuated vaccines like those used for the childhood diseases measles, mumps, rubella and chickenpox, in which a weakened or attenuated form of the virus that causes the disease is manufactured.

Because live-attenuated vaccines are so similar to the natural infection that they help prevent, a strong and long-lasting, even life-time immune response can be produced.

In a 2018 scientific article, Dr Baric offered a strategy for the development of a broad-spectrum, live-attenuated vaccine for coronaviruses.

Baric also identified the inherent danger of live-attenuated virus vaccines that they have been shown to revert back to their original pathogenic structure after administration to a recipient.

That risk is exponentially increased for self-spreading vaccines, which are essentially genetically engineered live-attenuated vaccines designed to move through populations in the same way as viruses, but rather than causing disease, conferring protection.

In my two previous articles, here and here, I cited evidence supporting the argument that the COVID-19 virus originated in connection with Chinas vaccine development program, in which a live-attenuated virus may have reverted to its deadly form after a human infection and then leaked from laboratory containment.

Given the mounting evidence, a non-natural origin for the COVID-19 pandemic demands investigation.

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