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Thomas Baldwin is Assistant Professor at North Dakota State University, Doctor of Philosophy in Plant Pathology, researching the function of RNA interference and how small RNA plays a role in host-pathogen interactions. He was featured in Part 26 of my The Corona Conspiracy as a critic of virus deniers Andrew Kaufman and Tom Cowan.

Understanding Virology for Skeptics

Unveiling the Scientific Realm
Through Scientific Rebuttal to
Five Virus Denier Arguments

Thomas Baldwin

The intricacies of life and evolution have captivated our understanding since Darwin's time, leading us to explore the profound mechanisms that shape species survival and proliferation. With advancements in inquiry and sophisticated methodologies, our comprehension has deepened. Amidst our exploration of nature, medicine, and human well-being, an intriguing group of entities challenges our conventional notions of life itself: viruses. These remarkable organisms distill the fundamental components essential for replication to an extraordinary minimum. They defy our established definitions of life, prompting us to reconsider our understanding. Viruses are obligate intracellular parasites. Their biology allows them to harness the machinery of host cells to reproduce, subsequently disseminating to infect new cells and organisms. Though intricate in their interactions and the diseases they incite, the undeniable existence of viruses and their capacity to induce disease across all life forms stand as scientifically incontrovertible realities. The emergence of the viral concept wasn't an arbitrary decree but a logical explanation rooted in observations across environments, human and animal health, cellular biology, and pathology. In the realm of science, theory validity rests upon its predictiveness and ability to be tested. The virus theory meets these criteria. The observable particles under the microscope correlate with observed proteins coded in the viral genome, and both aspects have been independently and repeatedly confirmed through replicable experiments. This convergence and alignment of results represent the most robust form of scientific evidence, reinforcing the authenticity of the viral phenomenon.

Thomas S. Cowan

Virus denial constitutes a distortion of the scientific method, deviating from the foundational principles of virology that stem from meticulous observation and rigorous experimentation. It emerges from a stance of skepticism toward established scientific knowledge, aligning itself with contrarian counter-culture sentiments and counter-establishment sentiments. Consequently, virus deniers fail to amalgamate observations into a coherent theory. Instead, they resort to piecemeal explanations solely aimed at challenging virus theory, devoid of predictive capabilities, falsifiable hypotheses, or cross-disciplinary applications. Analogous to the flat-earth and creationist movements, proponents of virus denial evade comprehensive experimentation, opting to selectively extract complex concepts out of context to pseudo scientifically bolster their counter-arguments. While their assertions might resonate with those unversed in scientific methodology, such arguments swiftly crumble when presented to a group of trained scientists. Just as there are no flat-earth astronauts or creationist pioneers in the fields of life origins and taxonomy, virus deniers do not contribute to advancements in cellular biology or organismal biology. Scientifically speaking, their ideas remain stagnant, only serving as tools for those external to the scientific community who seek to reinforce particular worldviews.

Scientists have been presented with five arguments posed by virus deniers, aimed at sowing seeds of doubt. The deliberate inclusion of terms like "properly controlled" and "normal way" creates a lack of falsifiability, preventing clear criteria for assessment. The definition of a "proper control" varies with each experiment, but in this context, it leaves room for potential non-control scenarios, enabling virus deniers to assert victory without justifiable reasons or supporting evidence for the necessity of such controls. Nevertheless, addressing these five arguments comprehensively, while anticipating a lack of good faith response from virus deniers, is essential to prevent the propagation of harmful misinformation. Below, a comprehensive response to these arguments is provided, acknowledging that virus deniers are likely to engage in bad faith arguments to perpetuate their narrative rather than contribute to the advancement of cellular biology science. Each scientific response is supported by multiple papers, demanding any one argument be shown in a single paper, when the argument contains multiple questions will be deemed a bad faith response.

The Virus Denier Arguments 1 and 2 share a common thread and can be effectively addressed with the following references. Their conclusions overlap in their quest to establish a point. In less complex terms, both Challenge 1, which explores "A properly controlled study showing sick people make well people (or animals) sick," and Challenge 2, focusing on "A properly controlled study showing the 'filterable fraction' of any biological fluid makes people or animals sick when exposed to it in a 'normal' way," are essentially inquiring if the infectious material can cause illness in both animals and humans. Curiously, they omit plants from their consideration, even though experiments involving plant viruses satisfy the criteria of causing disease through infectious material and being filterable[1],[2],[3]. The wealth of studies centered on animals and humans substantiating these postulates is substantial, encompassing diseases such as rabies[4], SARS[5], COVID-19[6], Polio[7], and numerous others.

These studies effectively fulfill both criteria 1 and 2, consistently showcasing the existence and transmission of various viruses. Adhering to the modified Koch's postulates, multiple research groups have successfully met the three criteria—encompassing isolating the virus from affected hosts, cultivating it within host cells, and validating infections. Notably, Virus Denier Challenge 2 contains two secondary queries, "filterability" and "normal way" of infection, which are inconsequential. The matter of "filterability" is rendered irrelevant based on metagenomic analyses and plating assays that demonstrate the isolation protocol generates a pure virus culture devoid of bacteria or fungi[8]. The inclusion of the phrase "normal way" employs a vague term, which functions as a weasel word, introducing ambiguity in the interpretation to cast doubt on the inoculation's administration process. This will not be addressed or it needs vastly more criteria and supporting literature to assert. The inclusion of the phrase "normal way" employs a vague term, which functions as a weasel word, introducing ambiguity in the interpretation of the inoculation's administration process.

Virus Denier Challenge number 3 has been comprehensively addressed through numerous meticulously controlled studies. These investigations have unequivocally demonstrated that the observed cytopathic effects (CPE) in viral culture experiments are unequivocally attributable to the specific virus in question. These studies encompass a range of controls, effectively ensuring that only the virus being investigated is accountable for the observed effects. However, the phrasing within the challenge, which states "A properly controlled study demonstrating that the CPE in a 'viral culture' experiment could have ONLY been caused by the virus in question," employs disingenuous tactics to foster uncertainty. The use of "could have ONLY" implies an insurmountable demand for controls, rendering falsifiability unattainable. These extraneous arguments are dismissed on the grounds that metagenomic sequencing exclusively identifies the virus genome in cultures manifesting phenotypic CPE, distinct from the mock controls[8].

Virus Denier Challenge number 4 questions the validity of electron microscopy (EM) studies by suggesting that any EM photo, regardless of method, has not been definitively proven to depict an isolated and purified virus. It's important to clarify that EM studies adhere to rigorous protocols, including purification techniques, to capture images of viral particles with absolute precision. These studies entail meticulous sample preparation, isolation, and purification steps, ensuring that the observed structures are indeed representative of viruses. The following publications have used a myriad of techniques including; fluorescence tagging, PCR, immunoblot, and a comprehensive array of modern sequencing technology, both long and short read sequencing.

The demand for EM photos to be proven as isolated and purified virus images raises a fundamental point about the scientific process. Scientific knowledge is built upon cumulative evidence, including thorough documentation of methodologies and peer-reviewed results. While no scientific observation is devoid of uncertainty, the collective body of evidence from properly conducted EM studies provides strong support for the identification of isolated and purified viral particles. Therefore, challenging the entirety of EM research based on the ambiguity of a single photo gravely misrepresents the robustness of the scientific methodology involved.

Virus Denier Challenge number 5 questions the origin of assembled "viral" genomes and demands that a properly controlled genome study demonstrates that all components of such genomes could only originate from the specific virus in question. While the challenge aims to raise doubts about viral genomics, it's crucial to consider the complexity of genetic evolution and variation. Genome studies involve comprehensive analyses of genetic sequences to understand relationships, mutations, and evolutionary origins. However, demanding absolute certainty in attributing all genome components to a single virus overlooks the natural genetic diversity and mutation processes that occur over time. Genetic variation is a common phenomenon in all organisms, including viruses, and the challenge's request for complete exclusivity overlooks the intricate interplay of genetic material within populations. While a single controlled genome study may not provide absolute certainty, the collective body of genetic research, coupled with comparative analyses and evolutionary insights, strengthens our understanding of viral genomes. Therefore, it's vital to approach genome studies with a nuanced understanding of the intricate genetic variation and evolutionary dynamics that transpire over time. Genomics, like all branches of biology, operates within the realm of stochastic science, where probabilities, uncertainty, and diverse influences interplay to shape the genetic landscape. Recognizing this inherent complexity fosters a more accurate comprehension of how genetic information evolves, diversifies, and adapts, contributing to a richer understanding of the intricate tapestry of life's genetic blueprint. Citing all publications that are sequenced and fully assembled would be a monumental task. Instead we cite the assembly of viral genomes and indefinitely link the sequences of 20 species of viruses known to cause human disease and 5 species that are plant, animal, and bacterial pathogens, such as duplodnaviria.

The wealth of research and comprehensive analyses within the realm of genomics is truly staggering. Our modern understanding of genomics, coupled with the support that have been developed, holds immense predictive potential for addressing an endless array of biological questions. For most individuals, grasping the intricate structures and functions of the genome that sustain life presents a challenge. As a point of comparison, consider the recent successful deployment of the James Webb Space Telescope—a monumental scientific feat that can peer back 13.5 billion years into the past. This achievement is akin to sequencing a whopping 4 million DNA base pairs in a single read. In the span of our lifetimes, it once required teams of researchers and potentially months of labor to generate just 0.000125% of that DNA record. While we may not possess a complete grasp of every aspect within this infinitely deep pool of knowledge, it is undeniable that we have made remarkable strides in unraveling the intricate mysteries that lie within.

The realm of genomics is a treasure trove of research and in-depth analyses that inspire awe. Our contemporary understanding of genomics is strengthened by robust support for meticulously developed models. This reinforcement comes from various disciplines such as proteomics, metabolomics, and a range of tests that establish the validity of genome assembly, genes, and pathways, collectively providing profound predictive power to unravel a vast spectrum of biological inquiries.

REFERENCES

1. "cDNA cloning of the complete genome of tobacco mosaic virus and production of infectious transcripts", pnas.org
2. "Potato virus X: A global potato-infecting virus and type member of the Potexvirus genus", bsppjournals.onlinelibrary.wiley.com
3. "Nucleotide Sequence of Cauliflower Mosaic Virus DNA", cell.com
4. "Airborne rabies encephalitis: demonstration of rabies virus in the human central nervous system", pubmed.ncbi.nlm.nih.gov
5. "Koch's postulates fulfilled for SARS virus", ncbi.nlm.nih.gov
6. "Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults", nature.com
7. "Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template", science.org
8. "The Architecture of SARS-CoV-2 Transcriptome", sciencedirect.com