Alternative Hypothesis to Communicable Disease-Causing Agents & Notes on Virology in relation to the No-Virus People

In response to Steve Kirsch's newsletter in friendly discussion with Patrick Gunnels

Hi Steve,

(PART 1) ALTERNATIVE HYPOTHESIS

Regarding your question, you said that your wife had COVID-19 because she was sick with a compatible Clinical Presentation and she tested positive for SARS-CoV-2, via Antigen Test, several times until she cleared the virus. She was also in previous contact with someone that also had COVID-19 and therefore you have established a Route Of Transmission. Then you got sick with a similar Clinical Presentation, via contact with you wife, and again, you tested positive in a similar manner with an Antigen Test. You also remarked that your wife lost her taste, which is associated with COVID-19 as a specific symptom, although, I must add, many other common respiratory illnesses can cause loss of taste and smell, but I will not focus on that. You were asking for an Alternative Hypothesis that doesn't require a Disease-Causing Agent.

Well, let's work a hypothesis here. Because the virus vs no-virus is nonsense to me, I will refer to Biological Structures and Disease-Causing Agents. Sometimes I will use the term virus for clarification. What I am going to dispute is the requirement of Communicable Disease-Causing Agents for the Etiology of your Clinical Presentation.

*First of all, regarding the Antigen Test. This test doesn't measure the presence of any Disease-Causing Agent. It measures the presence of antigens that react to antibodies via an immunoassay. Antigens are molecules or molecular structures, usually proteins, that are present in many different Biological Structures that can be recognized by the immune system.

Four Fundamentals of Immunoassay Quality

https://www.rndsystems.com/four-fundamentals-immunoassay-quality

Therefore, the Antigen Test, if we assume that it works properly and it is not a false positive, is measuring an immune response which is reactive to a certain Epitope Constellation. An Epitope is the part of an antigen that is recognized by the immune system, in this case, by antibodies.

I called it an Epitope Constellation because every antigen has many potential Epitope Regions and these Epitope Regions are conserved among different antigens from many different Biological Structures (e.g. the N proteins of Coronaviruses). In other words, antibodies are not specific and they cross-react with Epitope Constellations, which may be representative of a Clade of Biological Structures. I use the term Constellation in a sense similar to this paper:

Multiple Genome Constellations of Similar and Distinct Influenza A Viruses Co-Circulate in Pigs During Epidemic Events

https://pubmed.ncbi.nlm.nih.gov/28928365/

*To avoid discussions about the accuracy and error rate of Antigen Tests, I am going to assume that all three individuals in the Route of Transmission, You, Your Wife and "Patient Zero" also tested positive with a PCR test, and not only that, but samples where taken from the three of you and you were also positive via Viral Culture and Whole Genome Sequencing. Therefore, we "have", in this hypothesis, a very reasonable expectation for the presence of SARS-CoV-2 in the three of you.

IMPORTANT: Here I am not characterizing SARS-CoV-2 as a virus in the sense of a Disease-Causing Agent. I am characterizing SARS-CoV-2 as a Biological Structure which is observed as a correlation between a Culturable Material (in the Biological sense defined by Virologists) and the presence of a given Genome Constellation which is present in the sample of an individual, given that the proteins produced by the Consensus Sequence of this Genome Constellation have also been analyzed and they have been determined to be present in the sample at some point or in previous studies (e.g. presence of E, N, ORFs, S... proteins in the case of Coronaviruses). It is important to notice that Whole Genome Sequencing can be performed without the need for culturing the virus if you already have enough knowledge about the sequence you are looking for. It can be done directly from the sample extracted from an individual, and this genetic material can be present in a healthy individual in many instances (the so called "asymptomatic carriers").

Full Genome of Influenza A (H7N9) Virus Derived by Direct Sequencing without Culture

https://wwwnc.cdc.gov/eid/article/19/11/13-0664_article

Direct next-generation sequencing of virus-human mixed samples without pretreatment is favorable to recover virus genome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710016/

I have to repeat, the presence of these types of Genome Constellations and Biological Structures do not necessarily mean the presence of a virus in the sense of a Communicable Disease-Causing Agent. The dynamics of these Biological Structures cannot be directly observed and it is very difficult to infer from proxy measurements, therefore there is much unknown in relation to them. Most of them are known because they have been found in association with many different diseases. However we are starting to discover that they do have a significant, beneficial, and important role in many biological functions within the ecosystem.

The good viruses: viral mutualistic symbioses

https://pubmed.ncbi.nlm.nih.gov/21200397/

"Although viruses are most often studied as pathogens, many are beneficial to their hosts, providing essential functions in some cases and conditionally beneficial functions in others. Beneficial viruses have been discovered in many different hosts, including bacteria, insects, plants, fungi and animals. How these beneficial interactions evolve is still a mystery in many cases but, as discussed in this Review, the mechanisms of these interactions are beginning to be understood in more detail."

From many different studies, we have very reasonable empirical evidence that they do move within the environment, between individuals and between species in some instances. Their evolution and changes can be measured in a consistent way within a given population presenting different degrees of prevalence for each Genome of the Constellation of Genomes to which they belong to.

*Now Steve, you would say something like... [well you have already proof my point. These Biological Structures do transmit between individuals, they have been found in association with diseases, the three of us had them in our system and the three of us were sick via this route of transmission. Hence, they are the Disease-Causing Agent we are looking for, "Patient Zero" gave it to my Wife, and my Wife gave it to me! Problem solved!]

However that line of thinking is not correct. First of all, you need to know the background prevalence of these Biological Structures. Testing yourself when you are sick is a Bias Measurement. If you test a given population for a given period of time you will find the presence of these Biological Structures in many healthy individuals, although it is also the case that their presence is enhanced during a Disease Course with a Clear Clinical Presentation. The so called "Higher Viral Load". That is why I am saying, repeatedly, that some of them have been found In Association with a Disease. Thus the core of the issue is the difference between a Communicable Disease-Causing Agent (CDCA) and Biological Structures that have been found In Association with a Disease, which we could called, Disease Associated Biological Structures (DABS).

NOTE: From now on I will use this acronyms (CDCA) VS. (DABS)

MAIN SIMILARITIES BETWEEN (CDCA) & (DABS):

* Both can be transmitted within the environment and between individuals.

[It is important to notice however, that many Biological Signaling Pathways share this characteristic, therefore it is not uncommon in Biology and it is not directly related to the potential for communicable diseases.]

* Both are found In Association with a Disease.

[However, the very well known sentence, "Correlation doesn't mean causation" is something to remember here].

* Both may be shown to share elements that are harmful to the Body. For instance, in the case of SARS-CoV-2, the Spike Protein has been shown to be Cytotoxic.

[Again, we have to be careful here. These Biological Structures are in Equilibrium Within The Ecosystem, they are found In Association with a Disease and showing toxic characteristics, if and only if, their balance within the ecosystem is disturbed, which is a key component of the working hypothesis that I am trying to established here as an alternative explanation.]

MAIN DIFFERENCE BETWEEN (CDCA) & (DABS):

* CDCA are Communicable Causative Agents while DABS are transmitted within the environment, with a certain degree of prevalence within the population, NOT BEING the Causative Agent of a Disease.

[This difference is very important. DABS spread within the ecosystem, they transmit between individuals, however their transmission is not in direct correlation with the starting point of a Disease Course. In the CDCA paradigm this phenomena would be mistaken by the so called "Asymptomatic Transmission", which undermines their logic in my opinion. How can it be the Causative Agent if it doesn't initiate an equivalent Disease Course every time it is transmitted between individuals? To solve this fact they allude to the concept of Susceptibility To The Disease. However, and this is a key point, this would imply that this so called "Susceptibility" is an Ecosystemic Factor, within the individual, between the individual and the ecosystem, or within the ecosystem itself, that could, by itself, be the Etiological Factor we are looking for.]

Argument in favor of CDCA in relation to the Susceptibility factor: We could argue that this susceptibility factor becomes irrelevant once the "viral load" of the Causative Agent is high enough. In which case, all individuals exposed, will become severely ill.

Counterargument to first proposition: If you take a Biological Structure, self regulated by the ecosystem, and you put it out of balance by increasing its concentration ("load") in a certain individual... It is not the Biological Structure, the one that is acting as Causative Agent, but the disturbance itself that you are introducing in the ecosystem by doing that.

IMPORTANT: This point may seem, to some, a kind of game with semantics. However this is the key issue here. Your actions and responses to the environment and the ecosystem you are in are based on language, information that is shared according to given narratives. If we are talking about disturbances within the ecosystem as the Etiological Factor of a Disease that is prevalent within a population, the action that you will take in order to solve the problem will be very different from what you would otherwise do within the CDCA Paradigm of Thinking. Hence, it is not "just semantics", it has a consequence, and as we now know from the COVID-19 situation, it may be a very dramatic consequence.

Argument in favor of CDCA in relation to "A Communicable Disease-Causing Agent": One could argue that SARS-CoV-2 was created in a lab, that it was released, intentionally or not, to the Human Ecosystem, that it spread within the Population, and that it acts as the Causative Agent of COVID-19.

Counterargument to second proposition: We have to consider in the first place that this argument is very convoluted, it involves many definitions, many unknown factors, and it is directly related to our ability to accurately track Biological Structures, which is in fact very limited with our current technology. To avoid all those problems I am just going to propose an alternative example based on a simplified version of a hypothetical case:

Someone took stable Biological Structures from the Ecosystem and did so called "Gain of Function" with them in order for them to be Metastable within the Human Ecosystem. Then, those Biological Structures were released, intentionally or not, to the environment, and a Clinical Presentation of a "New Disease" (for simplicity I will consider it to be a "New Disease", even though it is not so simple) starts to appear within the Population. What is happening here? A Communicable Disease??

As I said before [this so called "Susceptibility" is an Ecosystemic Factor, within the individual, between the individual and the ecosystem, or within the ecosystem itself]. So... What is the Causative Agent? A very severe disturbance generated Within the Ecosystem Itself. The Biological Structure that has been generated is Metastable within its new ecosystem and it will be problematic until it becomes what many would called "Endemic". However it is not, still, a Communicable Disease-Causing Agent. In fact, in most instances, the transmission of these Biological Structures is selected in the direction of Endemicity, and that will happen very fast unless you introduce new disturbances within the Ecosystem (e.g. increased stress and immunosuppression via FearPorn, Mass Vaccination Campaigns to non-susceptible individuals...).

ALTERNATIVE HYPOTHESIS TO THE SPECIFIC CASE PRESENTED HERE:

Case: Patient Zero gave a CDCA to your wife and your wife gave it to you. The three of you showed signs of the presence of the Disease-Causing Agent called SARS-CoV-2 and your Clinical Presentation was compatible with a mild to moderate COVID-19 case.

Counter-case: As before, given that these statements are very convoluted, they involved many definitions, many unknown factors, perceptual factors, testing factors, misdiagnosis, anecdotal evidence, cognitive bias... In order to avoid all those issues I will simplify the case as follows:

An (A-type) Biological Structure, associated with a Clinically Defined Disease (A), was found in the three of you. The Clinical Diagnostic was equivalent in the three cases and compatible with Disease (A), where no other Disease Presentation is Symptomatically Compatible with Disease (A). There was a Temporarily Linked Route of Transmission.

As you can see I am simplifying the reality of the situation by a lot, which is kind of cheating to your advantage. However, even if I accept this simplification, especially the part that says "There was a Temporarily Linked Route of Transmission", which would imply no previous prevalence of the Biological Structure in any of you, prior to the Disease Course, I can still define the Case as follows...

A disturbance was created in the Ecosystem of Biological Structures related to the Human Condition. This disturbance induces the dysregulation of many constituents of the Ecosystem and in fact it propagates in order to seek equilibrium. Many elements are involved in this "Seeking for Equilibrium", not only (A-type) Biological Structures, however the most prevalent presentation of the net effect of this Ecosystemic Perturbation is the manifestation of Disease (A), were (A-type) Biological Structures will be present, even though They Are Not the Causative Agent. Susceptibility to this effect at any given time, by any given population would be the Etiological Factor related to the Route of Transmission, even though in most cases there was previous prevalence of (A-type) or closely related Biological Structures, that again, are not the Causative Agent, they are just tiedly involved in the disturbance that has been generated within the Ecosystem.

Therefore no CDCA was transmitted from Patient Zero to your wife and then to you as a Causative Agent of Disease (A). You experienced a disturbance in the equilibrium of the ecosystem you are in, given by internal causes (related to each individual), internal-external causes (related to the relationship between the individual and the environment), or external systemic causes (related to the ecosystem itself). In which case (A-type) Biological Structures are just a vector of Systemic Information within the ecosystem, and the solution to Disease (A) is not to cut the "Route of Transmission" of (A-type) Biological Structures, but to allow for the system to reach equilibrium minimizing the damage to the most susceptible elements/individuals. Additionally, one could redact new regulations that will make it impossible to create new systemic disturbances to begin with (e.g. Not doing Gain of Function research...).

(PART II) IN RELATION TO THE NO-VIRUS PEOPLE

FINAL NOTE: Regarding the issues described by the no-virus people. I honestly believe that some of their points have not been properly assessed by Modern Virology. You may rely on Whole Genome Sequencing on a regular basis because it is convenient, however, at least once, you absolutely must completely isolate the given Biological Structure and try to sequence it directly from the isolated sample. It doesn't need to be sequenced from nucleotide A to Z, because we cannot do that with our current technology, it just need to be sequenced, in a regular manner, from a sample that mainly contains particles with the density gradient where you would expect to find viruses after centrifugation. Which is exactly what they have to do in order to produce live-attenuated vaccines. It can be done:

Purification of viruses by centrifugation

https://www.researchgate.net/publication/278730267_Purification_of_viruses_by_centrifugation

"Purification of viruses from natural samples—Purifying viruses directly from natural marine and freshwater samples is similar in many respects to purifying a virus from a culture lysate; the goal in both cases is to separate the viruses from as much of the contaminating material as possible."

"If the purpose of the purification is to perform molecular analyses of the viral nucleic acids, the requirement for purity may be more stringent, and viruses may need to be separated from both cells and from dissolved nucleic acids. Although viruses usually outnumber cells in the plankton by over an order of magnitude, their genomes are so small that their nucleic acids make up only a small percentage of cellular and dissolved pools."

I don't see why they cannot seem to be able to do it. Why all those FOIA requests showing that SARS-CoV-2 has not been isolated in this manner? It clearly can be done and it should have been done at least once! Until they do not do that, the no-virus people will have a point that has to be solved.

NOTE: If it has been done, I am not aware of any paper in the Scientific Literature that clearly describes the results obtained from this process. Even though it should be something very simple to do, in principle.

Additionally, I see a whole lot of issues with the viral culture technique that they use. Let me give you an example:

I may think that I have Protozoa in my tap water. To test the water, I could take a sample and take a look with a regular microscope. What would happen? I most probably don't see anything, the water seems to be clean and if they are there, the amount of them is so tiny that I do not see them. What do I do then? I take some vegetable material and I sterilize it for 10 to 15 minutes in hot boiling water. Just to be sure that the Protozoa are not going to come from the vegetable material that I am going to use as a growth medium to culture the Protozoa from the tap water. So I put the sterilized vegetable material in the tap water and I take care that nothing external goes into it, to avoid contamination. In one to two weeks my culture of Protozoa will be full of Protozoa if they were in the tap water. Then I can take a sample, put it on my microscope and I will clearly see them swimming around. That is what virologist try to do with a virus culture.

The problem that I see is this. In my example with the Protozoa, my tap water was pretty much healthy, I could drink it and it will be OK. That is why I don't see the Protozoa if I do not culture them. If the water was sick however, I absolutely would be able to take a sample, directly, put it in my microscope, and see that it is full of microorganisms. I would directly know that I cannot drink that water, it would be dirty, green, it would smell bad...

So why in hell, as the no-virus people would say, is not happening the same with a tissue sample from a sick person, which is allegedly sick with a virus. The tissue will indeed look bad and it will smell bad, you would know that the tissue sample is not from a healthy person, that is a fact. Why then do I still need to culture the sample in a viral culture in order to see the viruses that are causing the damage? That is kind of alarming to me, it should be full of viruses popping out of the cells and there should be no need for any type of culture unless you want to have a huge amount of viruses in order to characterize them with additional methods (as it is shown in the next paper).

An Example of sample preparation and Virus Purification can be seen here:

Topography, spike dynamics and nanomechanics of individual native SARS-CoV-2 virions

https://www.biorxiv.org/content/10.1101/2020.09.17.302380v1

“Sample preparation

SARS-CoV-2 was isolated from the oropharyngeal swab of a laboratory-confirmed COVID-19 patient in Hungary and passed two times in VeroE6 cell line (European Collection of Authenticated Cell Culture, Salisbury, U.K.) in Dulbecco′s Modified Eagle′s Medium (Lonza, Basel, Switzerland) supplemented with 5% fetal bovine serum (EuroClone, Pero, Italy) and Cell Culture Guard (PanReac AppliChem, Darmstadt, Germany). To remove the disturbing effects of fetal bovine serum albumin, an additional passage was carried out in VP-SFM serum-free, ultra-low protein medium (Gibco, ThermoFisher Scientific) supplemented with L-glutamine (Sigma-Aldrich, Merck, Darmstadt, Germany). Four days after inoculation, when full cytopathic effects were observed, the virus-containing medium was collected add centrifuged (3000 x g) to remove debris. To concentrate the virus, the supernatant was ultracentrifuged (70,000 x g, 1.5 hours, 4°C) in 13.5-ml lockable plastic tubes using a Sorvall MTX-150 ultracentrifuge. The supernatant was removed and the pellet was resuspended in 100 µl VP-SFM. All sample preparation steps were performed in biosafety level-3 (BSL-3) conditions.”

Even more, for a viral culture to work, I have to weaken the cells of my culture, via starving them [IMPORTANT NOTE: I’ve been paying a little more attention to this point, that the no-virus people argue about and it seems that it is not so simple. Similar techniques are applied in cell cultures in general, not only in virology, and even within virology they do not seem to be universal. I have to research more on this but the argument seems to be invalid]. How is it that the virus is not able to infect healthy cells in a Petri Dish, with no immune system, no tissue mechanisms of protections, no nothing, but they can infect a healthy tissue in a healthy organ in a healthy individual with a properly functioning immune system and cause severe illness? That is another huge red flag to me! So something is not adding up in Virology at all, regarding so called “pathogenic viruses”. [IMPORTANT NOTE: Even if the starving of the cell cultures is not a valid argument, it is still important to notice that viruses are not easily culturable and some of them are not even culturable at all, which makes you wonder how can they “invade” a healthy organism. That seems to be very implausible still. They absolutely must have a constructive role in the ecosystem for them to be present. They are not “invaders”.]

References in relation to non-culturable viruses:

Reliability of non-culturable virus monitoring by PCR-based detection methods in environmental waters containing various concentrations of target RNA

https://pubmed.ncbi.nlm.nih.gov/23124739/

“In this study, we showed that the proportion of water sample concentrates used for one-step RT-PCR significantly influences false-negative findings of the non-culturable viruses.”

Identification of a new human coronavirus

https://www.nature.com/articles/nm1024

“First, some viruses do not replicate in vitro, at least not in the cells that are commonly used in viral diagnostics. Second, for those viruses that do replicate in vitro and cause a cytopathic effect (CPE), the subsequent virus identification methods may fail. Antibodies raised against known viruses may not recognize the cultured virus, and virus-specific PCR methods may not amplify the new viral genome.”

*************************** FINAL NOTE ***************************

This concerns must be addressed in a scientific manner. And if they have already been addressed, they must be presented to the public by Virologists in a humble way, not with arrogance and dismissiveness, which is what they tend to do regarding the no-virus people. That is prejudice and it is not helpful to anyone. Virology is a public good, not a club. All those questions and concerns must be answered.

In any case, this science is not at all as precise as they pretend it to be:

Choice of assemblers has a critical impact on de novo assembly of SARS-CoV-2 genome and characterizing variants

https://pubmed.ncbi.nlm.nih.gov/33822878/

“We showed that at least 09% (259/2873) of the variants present in the assemblies between MEGAHIT and metaSPAdes are unique to one of the assembly methods.

Conclusion: Our analyses indicate the critical role of assembly methods for assembling SARS-CoV-2 genome using short reads and their impact on variant characterization.”

Human Microbiome is a photograph by Russell Kightley/science Photo Library which was uploaded on October 30th, 2019.

https://fineartamerica.com/featured/9-human-microbiome-russell-kightleyscience-photo-library.html

Follow up on Steve Kirsch’s Newsletter comments section:

https://stevekirsch.substack.com/p/is-there-a-virus-round-1/comment/7937161#comment-7951654

(NEW COMMENT) https://stevekirsch.substack.com/p/if-viruses-dont-exist-then-how-can/comment/8119034