The Clonal Selection Antibody Theory (1957)

Immunology does not suffer from a lack of experimental data, but still some of the most elementary questions are undecided, and it is not yet possible to choose between instructive and elective theories.”

Joshua Ledergerg, Genes and Antibodies https://doi.org/10.1126/science.129.3364.1649

Every scientific theory relies on the scientific method. A scientist may make an observation and devise a hypothesis to explain that observation, then design an experiment to test that hypothesis. If the hypothesis is shown to be incorrect, the scientist will develop a new hypothesis and begin the process again. If the hypothesis is supported by the results of the experiment, it will go on to be tested again. If the hypothesis isn’t disproven or surpassed by a better explanation, the scientist may incorporate it into a larger theory that helps to explain the observed phenomenon and relates it to other phenomena, according to the Field Museum

A scientific theory is not the end result of the scientific method; theories can be proven or rejected, just like hypotheses. And theories are continually improved or modified as more information is gathered, so that the accuracy of the prediction becomes greater over time.

https://www.livescience.com/21491-what-is-a-scientific-theory-definition-of-theory.html

At the time that Frank MacFarlane Burnet proposed the Clonal Selection theory of antibody formation in 1957, there were a few different explanations floating about, including Burnet’s own Indirect Template theory which was suggested almost a decade earlier. They included:

  1. Side Chain Theory
  2. Direct Template Theory
  3. Indirect Template Theory
  4. Natural Selection Theory

Each of these theories proposed different ways antibodies formed based on the “scientific” evidence of the time. Naturally, Burnet saw the burning need to discredit his previous theory in order to throw a new one into the mix. To do so, he utilized Niels Jerne’s Natural Selection theory and reworked it so that he could cover-up the holes and lack of evidence in his previous attempt. Thus, the Clonal Selection theory was born and it has gone on to become the most widely accepted explanation for the formation of the unseen particles assumed to be within the blood. The acceptance of this “theory” is clearly pointed out by these first three sources, which use some interesting wording describing Burnet’s last contribution to the antibody narrative:

“Clonal selection theory is a scientific theory in immunology that explains the functions of cells of the immune system (lymphocytes) in response to specific antigens invading the body. The concept was introduced by Australian doctor Frank Macfarlane Burnet in 1957, in an attempt to explain the great diversity of antibodies formed during initiation of the immune response.[1][2] The theory has become the widely accepted model for how the human immune system responds to infection and how certain types of B and T lymphocytes are selected for destruction of specific antigens.[3]

https://en.m.wikipedia.org/wiki/Clonal_selection

“The clonal selection hypothesis is a widely accepted model for the immune system’s response to infection.

“clonal selection: An hypothesis which states that an individual lymphocyte (specifically, a B cell) expresses receptors specific to the distinct antigen, determined before the antibody ever encounters the antigen. Binding of Ag to a cell activates the cell, causing a proliferation of clone daughter cells.

The clonal selection hypothesis has become a widely accepted model for how the immune system responds to infection and how certain types of B and T lymphocytes are selected for destruction of specific antigens invading the body.”

https://bio.libretexts.org/Bookshelves/Microbiology/Book%3A_Microbiology_(Boundless)/11%3A_Immunology/11.07%3A_Antibodies/11.7C%3A_Clonal_Selection_of_Antibody-Producing_Cells

“In 1957, Burnet proposed that central tolerance to self-antigens occurred by clonal deletion of self-reactive lymphocytes [7]. However, as we will discuss, this model has been ‘updated’ on several occasions.”

https://www.cell.com/trends/immunology/fulltext/S1471-4906(04)00311-4

Notice the words hypothesis and model thrown about in these descriptions of what is considered to be the most widely accepted scientific theory for antibody production? What could they possibly be referring to? Let’s see if we can clear this up by looking at the definitions:

scientific hypothesis, an idea that proposes a tentative explanation about a phenomenon or a narrow set of phenomena observed in the natural world. 

https://www.britannica.com/science/scientific-hypothesis

scientific modeling, the generation of a physical, conceptual, or mathematical representation of a real phenomenon that is difficult to observe directly. 

https://www.britannica.com/science/scientific-modeling

scientific theory, systematic ideational structure of broad scope, conceived by the human imagination, that encompasses a family of empirical (experiential) laws regarding regularities existing in objects and events, both observed and posited. A scientific theory is a structure suggested by these laws and is devised to explain them in a scientifically rational manner.

https://www.britannica.com/science/scientific-theory

Putting it all together, Burnet’s Clonal Selection theory conceived of by the human imagination, which can be rejected just like any other tentative explanation otherwise known as a hypothesis, is the current model, which is a conceptual representation of a real phenomenon that is “difficult to observe directly.” This explanation obviously creates a bit of a problem. In order for this hypothesis/model/theory to be considered scientific, it must adhere to the scientific method:

“A theory is a carefully thought-out explanation for observations of the natural world that has been constructed using the scientific method, and which brings together many facts and hypotheses.”

https://www.fieldmuseum.org/blog/what-do-we-mean-theory-science

The scientific method requires the observation of a real phenomena in nature. In fact, this is the very first step:

  1. Observe a natural phenomenon
  2. Alternate hypothesis
    • Independent variable (the presumed cause)
    • Dependent variable (the observed effect)
    • Control variables
  3. Null hypothesis
  4. Test/experiment
  5. Analyze the observation/data
  6. Validate/invalidate hypothesis

It requires the use of a valid independent variable, i.e. purified/isolated particles assumed to be antibodies, to vary and manipulate in order to determine a cause and effect relationship. In other words, the independent variable must be something that has been shown to physically exist in reality. As antibodies have never been purified and isolated directly from humans in order to be used as a valid independent variable and these particles can not be observed directly in nature, none of the indirect experimental data generated and utilized to formulate these theories was scientific. None of the antibody “theories” adhered to the scientific method in order to develop the hypotheses which were used to craft the experiments that were needed to produce the data which was utilized to create the theory. They all started by presupposing the existence of the very entity they were trying to conjure up evidence for in order to formulate a theory to explain the effects seen as well as the shape and function of the presupposed entity for which they could not observe directly.

Basically, this is a long way of saying that we can exclude scientific from the definition of the word “theory” used to describe Burnet’s Clonal Selection as it is obvious that it did not adhere to the scientific method and is thus not scientific at all. Therefore, we can replace the scientific definition with the common definition:

theory, an idea that is suggested or presented as possibly true but that is not known or proven to be true

https://www.britannica.com/dictionary/theory

This can be applied to all antibody theories which amount to nothing more than dreamt up speculative fantasies crafted from non-scientific experimental data which combined human and animal blood with various chemicals to create a non-specific reaction in order to blame on invisible entities. These mad science experiments are obviously the exact opposite of a natural phenoma observed in nature. All antibody theories therefore start from a fraudulent foundation.

In any case, as the previous theories/models of this unseen entity were unscientific and could not hold up to scrutiny, they were eventually unceremoniously thrown out in favor of Burnet’s Clonal theory. For decades it was considered as the “truth” even though it was nothing but speculation masquerading as science. However, even the unscientific Clonal theory has being challenged recently. In 1992, Irun Cohen, an immunologist at the Weizmann Institute of Science in Israel who developed the theory of the immunological homunculus in 1989, wrote a paper challenging the Clonal Selection theory. Unfortunately, I was unable to aquire the whole paper. However, the abstract gives us an idea as to the grounds Cohen challenged the theory on:

The cognitive principle challenges clonal selection

“Here, Irun Cohen argues that the clonal selection paradigm is no longer a convenient paradigm for organizing thinking about the immune system. He contends that most immunologists now investigate questions for which the clonal selection paradigm makes no provision and that one of its major tenets is contradicted by the prevalence of natural autoimmunity. Instead, he proposes a cognitive paradigm.”

https://pubmed.ncbi.nlm.nih.gov/1476598/

In a page referencing the work of Cohen, further light can be shed on his criticisms as he claimed that the tenets of classic Clonal Selection are not compatible with the findings reported in a paper on the success of a therapeutic peptide vaccination. Cohen felt that the success of the clinical trial was compatible instead with the homunculus concept of autoimmunity:

DiaPep277 Peptide and Type 1 Diabetes

Raz I., Elias D., Avron A., Tamir M., Metzger M., Cohen I.R.
-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): A randomized, double-blind, phase II trial. The Lancet, 2001; 358: 1749-53.

“At the practical level, this paper shows that autoimmune destruction of beta cells in patients with newly diagnosed type 1 diabetes can be arrested by the administration of DiaPep277, a peptide fragment of the 60kDa heat shock protein molecule. Three subcutaneous injection of the peptide, 1 mg each in an oil vehicle, were effective. The optimal dose of peptide and the most effective schedule of injections remain to be worked out. Nevertheless, the confirmation of effectiveness and safety in continuing trials would indicate that immunologically specific treatment of autoimmune disease is feasible.

At the theoretical level, these results serve as a proof-of-concept in the controversy between contending theories regarding the basic organization of the immune system. The classical clonal selection theory holds that:

  1. Self-non-self discrimination is the aim of the immune system;
  2. Autoimmunity is deleted from the healthy repertoire of antigen receptors;
  3. Autoimmunity arises by accident;
  4. Autoimmune disease therapy requires blocking self-recognition, or removal of self-recognizing lymphocytes.

These tenets of classic clonal selection are not compatible with the findings reported in the paper. On the contrary, the success of the clinical trial of therapeutic peptide vaccination is compatible with the homunculus concept of autoimmunity. This theory includes the following ideas:

  1. The aim of the immune system is not to discriminate self from non-self, but to organize inflammation in a way that maintains, heals and, where possible, regenerates damaged cells and tissues; the healthy system is continuously responding to self.
  2. The healthy repertoire includes a high frequency of lymphocytes that recognize key self-antigens: the immunological homunculus.
  3. Autoimmune diseases arise from a failure of normal regulation, and the resulting diseases are predictably associated with collectives of particular self-antigens.
  4. The natural cure to autoimmune disease is to activate and reinstate the regulatory mechanisms built into the homunculus.

The paper demonstrates that a single peptide can indeed activate regulation; the immune system is best controlled by supplying the immune information the system is organized to seek. The immune system is a cognitive system.”

https://www.weizmann.ac.il/immunology/sci/CohenPage2.html

Irun Cohen’s visual representation of natural autoimmunity–the immunological
homunculus https://doi.org/10.1016/j.jaut.2007.07.016

In 2002, Arthur M. Silverstein, an American immunologist and science historian who has written extensively on the history of immunology, wrote a paper attempting to defend the Clonal Selection theory. However, in the paper, he noted the criticism of the Clonal Selection theory by Cohen and others as an obsolete and outdated theory and pointed to some very important questions that CST needed to answer which were largely unaddressed:

The Clonal Selection Theory: what it really is and why modern challenges are misplaced

“The Clonal Selection Theory (CST)2 of Macfarlane Burnet and David Talmage seems to be under fire currently from several directions. Irun Cohen, in considering the role of autoimmunity in the economy of the body, suggested that, “Progress in immunology appears to have rendered the clonal selection paradigm incomplete, if not
obsolete; true it accounts for the importance of clonal activation, but it fails to encompass, require, or explain most of the subjects being studied by immunologists today …”. Polly Matzinger has gone even further: based upon her view that the “danger theory” has negated Burnet’s classical view of self-nonself discrimination, she extends this to suggest that the entire clonal selection paradigm that has ruled immunology for some 35 years has been overthrown.”

“Even philosophers of science have occasionally blurred the important distinction between the core hypotheses of CST and the ancillary
hypotheses that may stem from it. In his book The Immune Self: Theory or Metaphor?, A. Tauber calls Burnet’s view of tolerance “…a cornerstone of his later immune theory [CST]”, and throughout appears to accept the various challenges to Burnet’s ideas on tolerance and self-nonself as challenges to the central meaning of CST. Again, in their book The Generation of Diversity, S. Podolsky and A. Tauber discuss the several challenges to Burnet’s idea of self-nonself and conclude that, “Specifically, we must ponder whether CST, as constructed by Burnet, Talmage, and Lederberg [sic!8] … is now being seriously challenged”. Kenneth Schaffner, in his elegant discussion of the philosophical bases of CST, Discovery and Explanation in Biology and Medicine, formally defines three levels of hypothesis in CST and actually assigns Burnet’s tolerance hypothesis to a secondary level. But even he sometimes seems to suggest that tolerance experiments may serve as tests of CST.

From instruction to selection

Between 1930 and the early 1960s, the accepted explanation for the large repertoire of antibody specificities was that antigen somehow acts as a template to transfer information to the globulin-producing mechanism. This was termed an “instruction theory” and was advanced in different forms. At a time when immunology was preoccupied with chemical approaches, and when little was known about how proteins are formed, these instruction theories seemed plausible. No matter that they could not explain such observations as the persistence of antibody formation, the accelerated and enhanced secondary response or what would later be termed affinity maturation.

Then in 1955, in the context of increasing interest in tissue transplantation, immunodeficiency diseases, autoimmunity and tolerance, Niels Jerne suggested that the information for all antibody specificities is inherent in the host and expressed as “natural” antibodies. Now the sole function of antigen was to select the matching antibody and transport it to the appropriate cells where, somehow, they would be stimulated to produce more of the same. Jerne’s idea attracted little support at the time; its surviving claim-to-fame lies in the fact that David Talmage and Macfarlane Burnet independently saw in its selectionist approach the seed of an interesting idea.”

Silverstein offered questions CST must answer that were largely unaddressed. I’m paraphrasing them here for length considerations:

  1. If a “Landsteiner-size” repertoire arises spontaneously, what is the mechanism for its generation?
  2. If a repertoire is generated randomly and somatically, why are destructive autoantibodies not formed against native antigens to engender immediate autoimmune disease?
  3. Is there more than one type of receptor on a single cell?
  4. If somatic mutation persists after clonal expansion, how can clonal specificity be maintained?
  5. How can interaction of antigen with a surface antibody receptor induce cell proliferation and differentiation?
  6. What determines and regulates which clonal daughters differentiate to form antibody and which survive as memory cells?

“Any valid theory of antibody formation (and that is what CST is) must satisfactorily explain these and other questions. However, the central theory need not fall just because its promulgator was wrong in proposing a mechanism to answer one of its subsidiary questions. Some of these questions address the “selection” component of CST, whereas others deal with the “clonal” component; the former might survive the disproof of the latter. It is curious that CST has been challenged based upon Burnet’s error in explaining self-nonself discrimination, but no one has suggested that CST might be challenged because Burnet was wrong about the mechanism for the generation of diversity, although these are hierarchically equal hypotheses. Yet self-nonself is chosen among all the other possibilities, for reasons that we will explore below.”

“Burnet became so involved with the question of self and with his explanation of the mechanism of tolerance that even he began to view it as an integral part and even a test of CST, rather than as merely a subsidiary question to be approached by trial and error. In discussing the foundations of CST, Burnet admitted that if immunologists are correct in doubting that “tolerance is wholly a matter of the absence of the immunocyte … an extensive reorientation [of CST] will become necessary”. No wonder that others might feel the same! (We might note also that Burnet came close to giving up on CST in 1962, when reports came in of two and even four different antibody specificities produced by a single cell; when Szenberg et al. found too many pocks on the chorioallantoic membrane of chick embryos injected with small numbers of lymphocytes (that is, the proportion of cells specific for MHC alloantigens appeared to be much too high)40; and when Trentin and Fahlberg found that a single clone of cells used to reconstitute a lethally irradiated mouse seemed able to form antibodies of different specificities.)”

“Given this wide-open theoretical terrain, it is no wonder that debate continues on such questions as a “big bang” versus the continuous generation of diversity, the relative roles of central versus peripheral mechanisms of tolerance, the number and type of signals required for one or the other response, whether autoimmunity is dangerous or beneficial (Cohen) and whether the immune apparatus evolved to recognize infectious pathogens (Cohn and Janeway), “danger” (Matzinger) or, following Jerne, “self” (Coutinho and Cohen).”

“In the end, however, we must not lose sight of the fact that the CST is only a theory of how antibodies are formed, not a theory of why they are formed.”

DOI:10.1038/ni0902-793

As can be seen, Burnet’s theory, while presented as the truth regarding antibody production and formation, is not without its detractors. Even Burnet himself waffled on the correctness of his own theory in 1962, stated in 1967 that it was incomplete and the terms were obscure and meaningless, and considered his work speculative in his own paper. The entire 1957 paper detailing his ideas is presented below:

A Modification of Jerne’s Theory of Antibody Production using the
Concept of Clonal Selection

There are three current theoretical interpretations of antibody production which, following Talmage (1957), may be referred to as the direct template theory in which the antigen serves as a template against which the specific pattern of the antibody is synthesized, the indirect template theory which postulates a secondary template incorporated into the genetic-synthetic processes of the antibody producing cells (Burnet, 1956), and the natural selection theory in which the antigen acts essentially by selection for excess production of natural antibody molecules of corresponding type (Jerne, 1955).

The two latter theories were devised primarily to account for two sets of phenomena for which the direct template theory seems quite irrelevant. The first is the absence of immunological response to “self” constituents and the related phenomena of immunological tolerance; the second is the evidence that antibody production can continue in the absence of antigen. Some means for the recognition and differentiation of potentially antigenic components of the body from foreign organic material must be provided in any acceptable formulation. In Burnet and Fenner’s (1949) account, a positive recognition of “self” material was ascribed to the presence of “self
markers” in all potentially antigenic
macromolecules, and corresponding recognition units in the scavenger cells of the body. At the time it was regarded as inconceivable that a mechanism could exist which would recognise in positive fashion all foreign material and no attempt was made to devise one, despite the fact that we have always recognised the clumsy character of the self-marker, self-recognition scheme.

It is the great virtue of Jerne’s hypothesis that it provides an approach to this alternative method of recognising self from not self. There is no doubt about the presence in all mammalian or avian sera of a wide range of reactive globulins which can legitimately be called “natural antibodies.” Jerne assumed that amongst these globulin molecules were all the possible patterns needed for specific immunological type reaction with any antigen, except for those patterns corresponding to body antigens which would be eliminated by in vivo absorption. When a foreign antigen enters the blood it unites, according to Jerne’s scheme, with one of the corresponding natural antibody molecules. The complex is taken up by a phagocytic cell in which the antigen plays no further part, but the antibody globulin provokes the production by the cell of a fresh crop of similar molecules which are liberated as antibody. If this basis is accepted, most immunological phenomena can be well described in terms of the theory. Its major objection is the absence of any precedent for, and the intrinsic unlikelihood of, the suggestion that a molecule of partially denatured antibody could stimulate a cell, into which it had been taken, to produce a series of replicas of the molecule.

Talmage (1957) has suggested that Jerne’s view is basically an extension of Ehrlich’side chain theory of antitoxin production and that it would be more satisfactory if the replicating elements essential to any such theory were cellular in character ab initio rather than extracellular protein which can replicate only when taken into an appropriate cell. Talmage does not elaborate this point of view but clearly accepts it as the best basis for the future development of antibody theory. He stresses the multiplicity of the globulin types that can be present in the blood and is profoundly sceptical of any approach which attempts to “unitarian” an interpretation of antibody. In his view properdin has as much right to be called an antibody as any other globulin.

Before receiving Talmage’s review we had adopted virtually the same approach but had developed it from what might be called a “clonal” point of view. This is simply a recognition that the expendable cells of the body can be regarded as belonging to clones which have arisen as a result of somatic mutation or conceivably other inheritable changes. Each such clone will have some individual characteristic and in a special sense will be subject to an evolutionary process of selective survival within the internal environment of the body.

It is believed that the advantages of Jerne’stheory can be retained and its difficulties overcome if the recognition of foreign pattern is ascribed to clones of lymphocytic cells and not to circulating natural antibody. The resulting formulation may be stated as follows:

The plasma-globulins comprise a wide variety of individually patterned molecules and probably several types of physically distinct structure. Amongst them are molecules with reactive sites which can correspond probably with varying degrees of precision to all, or virtually all, the antigenic determinants that occur in biological material other than that characteristic of the body itself. Each type of pattern is a specific product of a clone of mesenchymal cells and it is the essence of the hypothesis that each cell automatically has available on its surface representative reactive sites equivalent to those of the globulin they produce. For the sake of ease of exposition these cells will be referred to as lymphocytes, it being understood that other mesenchymal types may also be involved. Under appropriate conditions, cells of most clones can either liberate soluble antibody or give rise to descendant cells which can.

It is assumed that when an antigen enters the blood or tissue fluids it will attach to the surface of any lymphocyte carrying reactive sites which correspond to one of its antigenic determinants. The capacity of a circulating lymphocyte to pass to tissue sites and there to initiate
proliferation is now relatively well established (cf. Gowens, 1957; Simonsen, 1957). It is postulated that when antigen-natural antibody contact takes place on the surface of a lymphocyte the cell is activated to settle in an appropriate tissue, spleen, lymph node or local inflammatory accumulation, and there undergo proliferation to produce a variety of descendants. In this way preferential proliferation will be initiated of all those clones whose reactive sites correspond to the antigenic determinants on the antigen used. The descendants will include plasmacytoid forms capable of active liberation of soluble antibody and lymphocytes which can fulfill the same functions as the parental forms. The net result will be a change in the composition of the globulin molecule population to give an excess of molecules capable of reacting with the antigen, in other words the serum will now take on the qualities of specific antibody. The increase in the number of circulating lymphocytes of the clones concerned will also ensure that the response to a subsequent entry of the same antigen will be extensive and rapid, i.e. a secondary type immunological response will occur.

Such a point of view is basically an attempt to apply the concept of population genetics to the clones of mesenchymal cells within the body. It is clear that the internal environment involved is an exceedingly complex one and in all probability many factors will impinge on clones of antibody-producing cells from that environment. It is equally certain that inheritable changes (at the clonal level) will occur as a result of somatic mutation or of the still obscure processes responsible for differentiation during development of regeneration and repair.

It would be inappropriate to elaborate this view much further in a preliminary communication, but it should be immediately evident that it has highly relevant implications for the general function of the lymphocyte, for the fact that sensitization and homograft immunity reactions seem to be mediated by lymphocytes or other mesenchymal cells without liberation of classical antibody, and for recent findings of extremely rapid liberation of antibody from normal cells. A preliminary survey of a variety of pathological conditions which involve anomalous immune reactions also suggests that this cellular approach has greater relevance to the problems than any of the other hypotheses. These aspects will be elaborated in a more extensive contribution now in preparation.

One aspect, however, should be mentioned. The theory requires at some stage in early embryonic development a genetic process for which there is no available precedent. In some way we have to picture a “randomization” of the coding responsible for part of the specification of gamma globulin molecules, so that after several cell generations in early mesenchymal cells there are specifications in the genomes for virtually every variant that can exist as a gamma globulin molecule. This must then be followed by a phase in which the randomly developed specification is stabilized and transferred as such to descendant cells. At this stage, again following Jerne, any clones of cells which carry reactive sites corresponding to body determinants will be eliminated. The necrotic effect of the tuberculin on sensitived fibroblasts might be taken as a crude analogue of the process by which clones with unwanted reactivity can be eliminated in the late embryonic period with the concomitant development of immune tolerance.

The hypothesis has many of the same implications as the Burnet-Fenner and the Jerne theories. Its chief advantage
over the former is its relevance to the nature of normal antibodies including the red cell isoagglutinins and the simpler interpretation of tolerance to potential antigens experienced in embryonic life. Its advantages over Jerne’s theory are its capacity to cover homograft and related types of immunity as well as the production of classical antibody, and to eliminate the very unlikely assumption that entry of a globulin molecule into a cell will stimulate the cell to produce exact replicas of that globulin.

Despite the speculative character of much of the detail of this modification of Jerne’s theory–which might be referred to as the “clonal selection hypothesis”–it has so many implications calling for experimental inquiry that it has been thought justifiable to submit this preliminary account for publication.

DOI:10.3322/canjclin.26.2.119

In Summary:

  • Irun Cohen, an immunologist at the Weizmann Institute of Science, Israel, argued that the clonal selection paradigm is no longer a convenient paradigm for organizing thinking about the immune system
  • He contended that most immunologists now investigate questions for which the clonal selection paradigm makes no provision and that one of its major tenets is contradicted by the prevalence of natural autoimmunity
  • Cohen stated that the results of a diabetes drug trial served as a proof-of-concept in the controversy between contending theories regarding the basic organization of the immune system
  • Cohen argued that the tenets of classic clonal selection are not compatible with the findings reported in the paper
  • On the contrary, the success of the clinical trial of therapeutic peptide vaccination was compatible with the homunculus concept of autoimmunity, which states:
    1. The aim of the immune system is not to discriminate self from non-self, but to organize inflammation in a way that maintains, heals and, where possible, regenerates damaged cells and tissues; the healthy system is continuously responding to self.
    2. The healthy repertoire includes a high frequency of lymphocytes that recognize key self-antigens: the immunological homunculus.
    3. Autoimmune diseases arise from a failure of normal regulation, and the resulting diseases are predictably associated with collectives of particular self-antigens.
    4. The natural cure to autoimmune disease is to activate and reinstate the regulatory mechanisms built into the homunculus.
  • Cohen argued that the immune system is a cognitive system
  • In considering the role of autoimmunity in the economy of the body, he suggested that, “Progress in immunology appears to have rendered the clonal selection paradigm incomplete, if not obsolete; true it accounts for the importance of clonal activation, but it fails to encompass, require, or explain most of the subjects being studied by immunologists today …”.
  • Polly Matzinger has gone even further: based upon her view that the “danger theory” has negated Burnet’s classical view of self-nonself discrimination, she extends this to suggest that the entire clonal selection paradigm that has ruled immunology for some 35 years has been overthrown
  • In his book The Immune Self: Theory or Metaphor?, A. Tauber calls Burnet’s view of tolerance “…a cornerstone of his later immune theory [CST]”, and throughout appears to accept the various challenges to Burnet’s ideas on tolerance and self-nonself as challenges to the central meaning of CST
  • Again, in their book The Generation of Diversity, S. Podolsky and A. Tauber discuss the several challenges to Burnet’s idea of self-nonself and conclude that, “Specifically, we must ponder whether CST, as constructed by Burnet, Talmage, and Lederberg [sic!8] … is now being seriously challenged”.
  • Between 1930 and the early 1960s, the accepted explanation for the large repertoire of antibody specificities was that antigen somehow acts as a template to transfer information to the globulin-producing mechanism.
  • This was termed an “instruction theory” and was advanced in different forms
  • At a time when immunology was preoccupied with chemical approaches, and when little was known about how proteins are formed, these instruction theories seemed plausible
  • No matter that they could not explain such observations as the persistence of antibody formation
  • Niels Jerne suggested that the information for all antibody specificities is inherent in the host and expressed as “natural” antibodies
  • Jerne’s idea attracted little support at the time; its surviving claim-to-fame lies in the fact that David Talmage and Macfarlane Burnet independently saw in its selectionist approach the seed of an interesting idea
  • Arthur M. Silverstein, immunologist and historian, submitted questions CST must answer:
    1. If a “Landsteiner-size” repertoire arises spontaneously, what is the mechanism for its generation?
    2. If a repertoire is generated randomly and somatically, why are destructive autoantibodies not formed against native antigens to engender immediate autoimmune disease?
    3. Is there more than one type of receptor on a single cell?
    4. If somatic mutation persists after clonal expansion, how can clonal specificity be maintained?
    5. How can interaction of antigen with a surface antibody receptor induce cell proliferation and differentiation?
    6. What determines and regulates which clonal daughters differentiate to form antibody and which survive as memory cells?
  • Any valid theory of antibody formation must satisfactorily explain these and other questions
  • However, Silverstein suggested that the central theory need not fall just because its promulgator was wrong in proposing a mechanism to answer one of its subsidiary questions
  • Some of these questions address the “selection” component of CST, whereas others deal with the “clonal” component; the former might survive the disproof of the latter
  • CST has been challenged based upon Burnet’s error in explaining self-nonself discrimination
  • In discussing the foundations of CST, Burnet admitted that if immunologists are correct in doubting that “tolerance is wholly a matter of the absence of the immunocyte … an extensive reorientation [of CST] will become necessary”.
  • Burnet came close to giving up on CST in 1962, when reports came in of two and even four different antibody specificities produced by a single cell
  • Given this wide-open theoretical terrain, it is no wonder that debate continues on such questions such as:
    1. A “big bang” versus the continuous generation of diversity
    2. The relative roles of central versus peripheral mechanisms of tolerance
    3. The number and type of signals required for one or the other response
    4. Whether autoimmunity is dangerous or beneficial (Cohen)
    5. Whether the immune apparatus evolved to recognize infectious pathogens
  • In the end it is stated that we must not lose sight of the fact that the CST is only a theory of how antibodies are formed, not a theory of why they are formed
  • According to Burnet, there were three (actually four yet Burnet excluded Ehrlich’s Side-chain theory for some reason) theoretical interpretations of antibody production:
    1. The direct template theory
      • The antigen serves as a template against which the specific pattern of the antibody is synthesized
    2. The indirect template theory
      • Postulates a secondary template incorporated into the genetic-synthetic processes of the antibody producing cells
    3. The natural selection theory
      • The antigen acts essentially by selection for excess production of natural antibody molecules of corresponding type
  • The two latter theories were devised primarily to account for two sets of phenomena for which the direct template theory seems quite irrelevant:
    1. The first is the absence of immunological response to “self” constituents and the related phenomena of immunological tolerance
    2. The second is the evidence that antibody production can continue in the absence of antigen
  • In Burnet’s own Indirect Template theory, a positive recognition of “self” material was ascribed to the presence of “self markers” in all potentially antigenic macromolecules, and corresponding recognition units in the scavenger cells of the body
  • At the time it was regarded as inconceivable that a mechanism could exist which would recognise in positive fashion all foreign material and no attempt was made to devise one
  • Burnet admitted that they always recognised the clumsy character of the self-marker, self-recognition scheme
  • Burnet applauded Jerne’s Natural Selection hypothesis (odd he called it a hypothesis rather than a theory) as it provided an approach to this alternative method of recognising self from not self
  • Jerne assumed that amongst the globulin molecules considered “natural antibodies,” there were all the possible patterns needed for specific immunological type reaction with any antigen, except for those patterns corresponding to body antigens which would be eliminated by in vivo absorption
  • When a foreign antigen enters the blood it unites, according to Jerne’s scheme, with one of the corresponding natural antibody molecules
  • Burnet pondered that if this basis is accepted, most immunological phenomena can be well described in terms of the theory
  • However, its major objection is the absence of any precedent for, and the intrinsic unlikelihood of, the suggestion that a molecule of partially denatured antibody could stimulate a cell, into which it had been taken, to produce a series of replicas of the molecule
  • Talmage suggested that Jerne’s view is basically an extension of Ehrlich’s side chain theory of antitoxin production and that it would be more satisfactory if the replicating elements essential to any such theory were cellular in character ab initio rather than extracellular protein which can replicate only when taken into an appropriate cell
  • Talmage did not elaborate this point of view but clearly accepted it as the best basis for the future development of antibody theory
  • He stressed the multiplicity of the globulin types that can be present in the blood and was profoundly sceptical of any approach which attempts to “unitarian” an interpretation of antibody
  • In his view properdin had as much right to be called an antibody as any other globulin
  • In other words, Talmage didn’t want the unseen antibody to be locked into a definite descriptive box and felt there were many globulin types which could be called antibodies
  • Before receiving Talmage’s review, Burnet claimed he had adopted virtually the same approach but had developed it from what might be called a “clonal” point of view
  • This was simply a recognition that the expendable cells of the body can be regarded as belonging to clones which have arisen as a result of somatic mutation or conceivably other inheritable changes
  • Burnet believed that the advantages of Jerne’s theory (wait…is it a theory or a hypothesis…) could be retained and its difficulties overcome if the recognition of foreign pattern is ascribed to clones of lymphocytic cells and not to circulating natural antibody
  • The plasma-globulins comprise a wide variety of individually patterned molecules and probably several types of physically distinct structure
  • Amongst them are molecules with reactive sites which can correspond probably with varying degrees of precision to all, or virtually all, the antigenic determinants that occur in biological material other than that characteristic of the body itself
  • Each type of pattern is a specific product of a clone of mesenchymal cells and it is the essence of the hypothesis that each cell automatically has available on its surface representative reactive sites equivalent to those of the globulin they produce
  • It was assumed that when an antigen enters the blood or tissue fluids it will attach to the surface of any lymphocyte carrying reactive sites which correspond to one of its antigenic determinants
  • It was postulated (i.e. suggest or assume the existence, fact, or truth of something as a basis for reasoning, discussion, or belief) that when antigen-natural antibody contact takes place on the surface of a lymphocyte the cell is activated to settle in an appropriate tissue, spleen, lymph node or local inflammatory accumulation, and there undergo proliferation to produce a variety of descendants
  • Such a point of view was basically an attempt to apply the concept of population genetics to the clones of mesenchymal cells within the body
  • It was clear that the internal environment involved is an exceedingly complex one and in all probability many factors will impinge on clones of antibody-producing cells from that environment
  • Burnet felt that it would be inappropriate to elaborate this view much further in a preliminary communication
  • A preliminary survey of a variety of pathological conditions which involve anomalous immune reactions suggested that this cellular approach has greater relevance to the problems than any of the other hypotheses (back to hypotheses instead of theories again)
  • Burnet stated that his theory required at some stage in early embryonic development a genetic process for which there is no available precedent
  • He claimed that they have to, in some way, picture a “randomization” of the coding responsible for part of the specification of gamma globulin molecules, so that after several cell generations in early mesenchymal cells there are specifications in the genomes for virtually every variant that can exist as a gamma globulin molecule
  • In other words, one must use ones imagination in order for this “theory” to work
  • Burnet claimed that the hypothesis had many of the same implications as the Burnet-Fenner and the Jerne theories (it seems one can switch between hypothesis and theory interchangeably)
  • Burnet stated that its chief advantage over his former theory is its relevance to the nature of normal antibodies including the red cell isoagglutinins and the simpler interpretation of tolerance to potential antigens experienced in embryonic life
  • Its advantages over Jerne’s theory are its capacity to cover homograft and related types of immunity as well as the production of classical antibody, and to eliminate the very unlikely assumption that entry of a globulin molecule into a cell will stimulate the cell to produce exact replicas of that globulin
  • Due to the speculative character of much of the detail of his modification of Jerne’s theory– Burnet referred to his latest as the “clonal selection hypothesis”

In 2007, Arthur M. Silverstein participated with a few other esteemed immunologists in reflecting back on the 50 year impact of the Clonal Selection “theory.” In it, he explained some of the opposition to CST and offered an ominous warning for what had to occur in order for the speculative hypothesis masquerading as a theory to be universally accepted by the immunology community:

Reflections on the clonal-selection theory

“There were two types of opposition to the CST, one early and continued, and the other of more recent vintage. The first was the resistance to this biological theory on the part of the chemically oriented immunologists who had introduced and believed in the instructionist theories of antibody formation that the CST replaced. Many of these immunologists chose to disregard the CST, continuing their physico-chemical studies of antibody and antigen (such as David Pressman, a student of Linus Pauling). Others sought to disprove it (such as Dan Campbell, also a Pauling student, who searched for persisting antigen, and Alain Bussard, who wrote a highly entertaining philosophical challenge to the CST). Some (like Elvin Kabat and Fred Karush) made peace with it. The rest (like Haurowitz and Bussard) never gave in. It was ever thus, as Thomas Kuhn pointed out that the full acceptance of a radically new paradigm occurs only when believers in the old one die out!”

doi: 10.1038/nri2177

According to Silverstein, in order for Frank MacFarlane Burnet’s 1957 Clonal Selection to be universally accepted, the old guard opposing it needs to die out. For whatever reason, Burnet’s storytelling happened to be the last one standing in a long line of theories about the formation and function of antibodies, even though it is still being challenged today. However, calling any of the proposed explanations which came before or after a scientific theory is completely unjustified as not a single one ever used evidence built from the scientific method. In no instance was any natural phenoma ever observed. Combining human and animal blood with various substances in a lab is not a natural phenoma and claiming the resulting effect has significance as to what occurs inside the human body is beyond ridiculous. At no point was a valid independent variable of purified and isolated particles assumed to be antibodies ever observed in order to determine cause and effect nor the form and function of the theorized entities. The idea of antibodies existed first in order to attempt to explain the lab-created effects. Without the direct evidence of these particles in the blood of humans, all of the hypotheses and all of the experimental data used to devise the competing theories amount to nothing but unscientific pseudoscience propping up the imagination of the interpretor. The resulting theories are fictional narratives explaining fictional entities.

If these theories are identified for what they truly are, which is an accumulation of guesswork, hunches, assumptions, and suppositions cobbled together into a fantastical narrative, there would be no problem. If people need to believe in invisible entities belonging to the realm of the imagination in order to have an explanation to justify their belief in a perceived immunity from invading boogeymen, so be it. The problems arise when these exercises in creative writing are presented as the truth rather than the science fiction that they most certainly are. When these stories are used to promote dangerous medical treatments and to determine one either free of or infected with a “deadly pathogen,” that is where the line needs to be drawn. We can not allow the wool to be pulled over our eyes any longer while pseudoscience is being presented as science and fiction is presented as truth. It is far past time to sound the alarm and shine the spotlight on these fraudulent practices before the narrative solidifies further as the truth in the minds of our youth.

26 comments

  1. Mike it’s so generous of you to persistently work on the exposè of the fraudulent tenets of virology. Great work once again! I wish there had been an alternative world– like Alice’s wonderland kind of world– where each person of the whole wide world was able to see the distinction between mass brainwashing, propaganda, deception on one side and truth, objective reality, scientific reasoning and logic on the other side. I think the first thing that might’ve happened is social network platforms such as yours would absolutely take over the public attention from the never ending hoaxers of mainstream media. Keep up the brilliant work mate.

    Liked by 2 people

    1. Thank you for the kind words and support! 🙂 I honestly feel compelled to continue. I always wanted to have this kind of information easily available when I started unraveling the insanity 5 years ago. I had many resources but they were not easy to find nor access and each had a different piece of the puzzle. It is my intention to make the search for information easier on people that are either just beginning this journey or are looking to deepen their understanding. My hope is that people will not just take my word but will read these sources and come to their own conclusions as well. This way, we can all learn and grow together. I will continue to do my part in exposing this madness.

      Liked by 2 people

  2. Fabulous! Wish you could know how much I appreciate and learn from your ViroLIEgy posts, Mike. I don’t like to reply too often as you must get hundreds of responses (Yikes!), some of which likely inspire great thinking and discussion. Still, I want you to know of my gratitude every once in awhile. ❣️ Cathleen

    >

    Liked by 2 people

    1. Thanks so much Cathleen! I am always happy to hear that the posts are of value. 🙂 I enjoy the discussions here and elsewhere. It helps me to learn and grow as well. We are all able to learn and grow together which is truly an amazing thing. While the internet and social media has been a hindrance in some ways, it has definitely been a blessing in others. We are able to share information in ways we never could in the past. I’m happy to be able to do my part to help share this information!

      Liked by 1 person

  3. I hope some people are keeping records of this content. This is crucial research unraveling each pillar of the paradigm in turn.

    “If these theories are identified for what they truly are, which is an accumulation of guesswork, hunches, assumptions, and suppositions cobbled together into a fantastical narrative, there would be no problem.”

    To me, “We’re doing the best we can” is the most insidious appeal of all. If the best they can do is guesswork, then they should put giant flashing lights on their papers warning any doctor, journalist, or public health official that it would be utter folly to base anything on these fantastical suppositions. Or how about stamping each page with “FOR ENTERTAINMENT PURPOSES ONLY” until you actually have something based on the scientific method? That’s a norm I would introduce in science. Ideas are welcome, but presenting ideas as solid conclusions is madness.

    Liked by 1 person

      1. I think some would be less averse to it that it would seem. The largest part of the problem is the hyperspecialization and Chinese whispers game that’s played where someone will publish something that should be understood as conjecture and others will take it as fact because they can cite their source. A kind of security by obscurity or argument by intimidation (by which I mean they know most people won’t check the references, and those that do will have too roundabout an argument to make against their confident one). Of course it doesn’t have to be just a two-step process like that; it can be three, ten, or even a hundred steps, making the ground truth much harder to ferret out.

        Liked by 2 people

      2. Exactly. Research is built upon previous research that was speculative in nature and never independently validated by reproducing/replicating the results. The scientific method is rarely, if ever, applied. Future researchers cite the work which will be cited by others which propagates and perpetuates the fraud further and further down the line. It becomes a tangled mess of a web to try and unweave.

        Liked by 1 person

  4. Hi Mike,

    While you’re doing antibodies how can I send you four files from 1935? All written by Alfred Sabin and reporting his experiments on how antibodies actually work. Worthy of your attention I think.

    Regards,

    Val

    Liked by 1 person

  5. And there goes more of the antibody edifice. Thanks, Mike.

    A related question: Antigen tests are now being presented as a “superior” alternative to the PCR test. I had a “truth activist” today tell me that she knows she had Covid because she got sick and had a positive antigen test, which a health practitioner friend of hers said was more accurate. This was in response to me and someone else saying that there is no proof of the virus. I’m having problems finding anything on antigen tests on this site, i get the antibodies article series and stuff on the PCR test when i do “search.” Did you ever do something specific about antigen tests? I know Rosemary Frei did one late last year, stating it was so bad the PCR was used to check it, as bad as it is. And of course, neither test has ever been calibrated with an actual virus, required for actual antibodies. So there is no way she and her friend are right, but just wondering if you had some additional “ammo.”

    Like

    1. Hi Jeffrey,

      I have not done an article specifically on antigen tests yet. I did some FB posts on them in the past but I have not yet done a specific article related to them here. They are definitely not as “accurate” as PCR (granted, none of the tests are accurate). I will provide some info from my FB posts here which may help. I had to capitalize on my posts to emphasize certain points as there is no bold function on FB.

      A key argument to support frequent use of antigen tests is that they accurately predict when a person with COVID-19 is infectious, HOWEVER THERE ARE LIMITED DATA TO SUPPORT THIS. It is true that antigen tests are less sensitive than high-quality molecular tests, which can remain positive for a prolonged period of time. HOWEVER, IT IS NOT CLEAR THAT ANY TEST, MOLECULAR OR ANTIGEN-BASED, CAN PREDICT WHEN AN INDIVIDUAL IS INFECTIOUS. In fact, according to its instructions for use, the BinaxNOW COVID-19 test was found to be positive in 83% of specimens with low levels of virus, as determined by a molecular test. Does this mean that the test was overly-sensitive in these cases? WE SIMPLY DO NOT KNOW. Other antigen tests have been found to be negative for samples with low levels of virus, as determined by a comparator molecular test. ASSUMING THAT ALL ANTIGEN TESTS CAN ACCURATELY PREDICT WHETHER SOMEONE WITH COVID-19 IS INFECTIOUS IS AN OVER SIMPLIFICATION when the complex course of disease is still not known, AND THERE ARE VARIABLE CHARACTERISTICS BETWEEN TESTS. Each test would need to be assessed separately.”

      https://asm.org/Articles/2020/November/SARS-CoV-2-Testing-Sensitivity-Is-Not-the-Whole-St

      The Case against Rapid Mass Testing part 2:

      “What is already known about this topic?

      Antigen tests for SARS-CoV-2 are inexpensive and can return results within 15 minutes, BUT TEST PERFORMANCE DATA IN ASYMPTOMATIC AND SYMPTOMATIC PERSONS ARE LIMITED.

      What is added by this report?

      Compared with real-time reverse transcription–polymerase chain reaction (RT-PCR) testing, the Sofia antigen test had a sensitivity of 80.0% and specificity of 98.9% among symptomatic persons; ACCURACY WAS LOWER (sensitivity 41.2% and specificity 98.4%) WHEN USED FOR SCREENING OF ASYMPTOMATIC PERSONS.

      What are the implications for public health practice?

      TO ACCOUNT FOR REDUCED ANTIGEN TESTS ACCURACY, confirmatory testing with a nucleic acid amplification test (e.g., RT-PCR) should be considered AFTER NEGATIVE ANTIGEN TEST RESULTS IN SYMPTOMATIC PERSONS AND POSITIVE ANTIGEN TEST RESULTS IN ASYMPTOMATIC PERSONS.”

      “These tests have been used at U.S. colleges and universities and other congregate settings (e.g., nursing homes and correctional and detention facilities), where serial testing of asymptomatic persons might facilitate early case identification (3–5). HOWEVER, TEST PERFORMANCE DATA FROM SYMPTOMATIC AND ASYMPTOMATIC PERSONS ARE LIMITED.”

      “Virus culture was attempted on all antigen-positive or real-time RT-PCR–positive specimens. Among 871 (79%) paired swabs from asymptomatic participants, THE ANTIGEN TEST SENSITIVITY WAS 41.2%, specificity was 98.4%, and in this population THE ESTIMATED POSITIVE PREDICTIVE VALUE (PPV) WAS 33.3%, and negative predictive value (NPV) was 98.8%. Antigen test performance was improved among 227 (21%) paired swabs from participants who reported one or more symptoms at specimen collection (sensitivity = 80.0%; specificity = 98.9%; PPV = 94.1%; NPV = 95.9%). VIRUS WAS ISOLATED FROM 34 (46.6%) OF 73 ANTIGEN-POSITIVE OR REAL-TIME RT-PCR–POSITIVE NASAL SWAB SPECIMENS, including two of 18 that were antigen-negative and real-time RT-PCR–positive (false-negatives). The advantages of antigen tests such as low cost and rapid turnaround might allow for rapid identification of infectious persons. HOWEVER, THESE ADVANTAGES NEED TO BE BALANCED AGAINST LOWER SENSITIVITY AND LOWER PPV, ESPECIALLY AMONG ASYMPTOMATIC PERSONS. Confirmatory testing with an FDA-authorized nucleic acid amplification test (NAAT), such as RT-PCR, should be considered after negative antigen test results in symptomatic persons, and after positive antigen test results in asymptomatic persons (1).”

      “At specimen collection, 227 (20.7%) participants reported experiencing one or more COVID-19 symptoms, AND 871 (79.3%) REPORTED NO SYMPTOMS.”

      “Among 227 paired specimens from symptomatic participants, 34 (15.0%) were antigen-positive, and 40 (17.6%) were real-time RT-PCR-positive.”

      (Only 15-17.6% positive out of 227 Symptomatic?!?!)

      “Sixteen paired swabs were antigen-positive and real-time RT-PCR–negative (i.e., false-positive), INCLUDING 14 (66.7%) OF 21 POSITIVE ANTIGEN RESULTS FROM ASYMPTOMATIC PARTICIPANTS and two (5.9%) of 34 from symptomatic participants.”

      “Second, GIVEN THE LIMITATIONS OF RT-PCR, SOME FALSE-POSITIVE ANTIGEN TEST RESULTS MIGHT REPRESENT TRUE INFECTIONS NOT IDENTIFIED BY RT-PCR.”

      “† Specimens were used to perform a LIMITING-DILUTION INOCULATION OF VERO CCL-81 CELLS, and cultures showing evidence of cytopathic effect (CPE) were tested by real-time RT-PCR for the presence of SARS-CoV-2 RNA. Viral recovery was defined as any culture in which the first passage had an N1 Ct at least twofold lower than the corresponding clinical specimen.”

      (Typical cell culture goo, no “virus” isolated and just using CPE to determine a “virus” is present in said goo).

      “VIRUS WAS RECOVERED FROM 34 (46.6%) OF 73 POSITIVE SPECIMENS, including 32 (82.1%) of 39 specimens with concordant positive results and two (11.1%) of 18 with false-negative antigen results; no virus was recovered from 16 specimens with false-positive antigen test results. THE TWO SPECIMENS WITH FALSE-NEGATIVE ANTIGEN RESULTS THAT WERE CULTURE-POSITIVE were from two symptomatic participants who had specimens collected at day 2 and day 4 after symptom onset.*”

      “Ct values from real-time RT-PCR WERE ONLY COMPARED FOR SPECIMENS COLLECTED AT UNIVERSITY A that were analyzed with the CDC 2019-nCoV real-time RT-PCR diagnostic panel for detection of SARS-CoV-2.”

      https://www.cdc.gov/mmwr/volumes/69/wr/mm695152a3.htm

      In Summary:
      -Antigen test performance data in symptomatic/asymptomatic individuals is limited
      -Antigen “accuracy” is lower in asymptomatic individuals
      -PCR should be used to confirm negative symptomatic results and positive asymptomatic results in Antigen tests
      -“Virus” was only “isolated” from 34 of 73 samples – less than half!
      -Only 15-17.6% of the 227 symptomatic cases were positive
      -Given PCR limitations, some false-positive antigen results may in fact be “true” positives MISSED BY PCR.

      Rapid Antigen Testing has massively increased since September 2020, right as “positive” cases increased with their use… 🤔

      From the November FDA WARNING for Rapid Antigen Tests:

      “The U.S. Food and Drug Administration (FDA) is alerting clinical laboratory staff and health care providers THAT FALSE POSITIVE RESULTS CAN OCCUR WITH ANTIGEN TESTS, including when users do not follow the instructions for use of antigen tests for the rapid detection of SARS-CoV-2. Generally, antigen tests are indicated for the qualitative detection of SARS-CoV-2 antigens in authorized specimen types collected from individuals who are suspected of COVID-19 by their healthcare provider within a certain number of days of symptom onset. THE FDA IS AWARE OF REPORTS OF FALSE POSITIVE RESULTS ASSOCIATED WITH ANTIGEN TESTS USED IN NURSING HOMES AND OTHER SETTINGS and continues to monitor and evaluate these reports and other available information about device safety and performance.

      The FDA reminds clinical laboratory staff and health care providers ABOUT THE RISK OF FALSE POSITIVE RESULTS WITH ALL LABORATORY TESTS.”

      “The package insert for tests also includes instructions about reading the test results, including the appropriate time to read the results. READING THE TEST BEFORE OR AFTER THE SPECIFIED TIME COULD RESULT IN FALSE POSITIVE OR FALSE NEGATIVE RESULTS.”

      “BE CAREFUL TO MINIMIZE THE RISKS OF CROSS-CONTAMINATION WHEN TESTING PATIENT SPECIMENS, WHICH CAN CAUSE FALSE POSITIVE RESULTS. Insufficient cleaning of the workspace, insufficient disinfection of the instrument, or inappropriate use of protective equipment (for example, failing to change gloves between patients) CAN INCREASE THE RISK OF CROSS-CONTAMINATION BETWEEN SPECIMENS WITH SUBSEQUENT FALSE POSITIVE RESULTS.”

      “AS DISEASE PREVALENCE DECREASES, THE PERCENT OF TEST RESULTS THAT ARE FALSE POSITIVES INCREASE.”

      https://www.fda.gov/medical-devices/letters-health-care-providers/potential-false-positive-results-antigen-tests-rapid-detection-sars-cov-2-letter-clinical-laboratory

      🤣 When you try to make the case for the rapid saliva-based antigen test by trashing the PCR test and you end up destroying them both 🤣

      “At first blush, you might reasonably dismiss the rapid, saliva-based antigen assay for coronavirus. What possible purpose can a test serve in a pandemic IF IT MISSES, SAY, 30 OF EVERY 100 INFECTIONS IT ENCOUNTERS, leaving those cases undetected, untreated, and uncontained? What good is a test that CREATES THAT MUCH FALSE REASSURANCE and causes exactly the wrong people to relax their adherence to social distancing? WHO WOULD EVEN THINK OF USING SUCH A TEST IN A HOSPITAL SETTING, WHERE A FALSE NEGATIVE RESULT MIGHT IMPERIL THE SAFETY OF HEALTH CARE WORKERS?

      You wouldn’t be alone. THE FAILURE OF THE ANTIGEN-BASED ASSAY TO MATCH THE DIAGNOSTIC ACCURACY of the gold-standard test you are probably familiar with—the laboratory based, reverse-transcription polymerase chain reaction (PCR) nasal (or nasopharyngeal) swab—is why the Food and Drug Administration (FDA) HAS BEEN RELUCTANT TO APPROVE IT FOR SALE IN THE U.S.

      But what if we re-framed the narrative? What if we instead asked what possible prevention purpose a PCR test can serve in a pandemic if it RETURNS POSITIVE RESULTS IN PEOPLE WHO HAVE ALREADY CLEARED THE VIRUS AND POSE NO RISK OF FURTHER TRANSMISSION? What good is a PCR test that IDENTIFIES NON-INFECTIOUS INDIVIDUALS as candidates for isolation and quarantine? Who would even think of using PCR for outbreak containment IF IT SENDS UP SO MANY FALSE ALARMS, leading contact tracers on so many wild goose chases, and undermining public confidence in the role of testing to keep us safe?”

      Contrast that with PCR, WHOSE PERFORMANCE BARELY DEPENDS AT ALL ON VIRAL LOAD. In principle, PCR can detect just a few copies of viral RNA. PCR starts to pick up the scent on Day 2 and continues to return positive results for as many as 6-12 weeks after exposure. That’s great if you’re interested in knowing if someone was infected in the past several weeks to months; but it’s a problem if you are interested in knowing if someone is infectious right now. The PCR CONTINUES TO PRODUCE POSITIVE RESULTS long after a person has ceased to pose any real risk of transmission to others, some data say up to 12 weeks longer!

      As a test of infectiousness, THE PCR TEST IS FAR TOO PRONE TO FALSE-POSITIVES. These false positives clog up the testing and contact tracing infrastructure and needlessly ground a lot of people who pose no transmission risk to others. PCR IS THE WRONG TOOL for the surveillance job.”

      “Rapid, saliva-based antigen testing is an essential weapon in the fight to resume many of the activities and reopen many of the venues that comprise what we used to call “normal life.” It is practical, convenient, cost-effective, and easily scaled. IT IS TIME TO STOP ASKING WHAT POSSIBLE USE WE MIGHT HAVE FOR A TEST WITH A 30 PERCENT FALSE NEGATIVE RATE.”

      https://www.healthaffairs.org/do/10.1377/hblog20200909.430047/full/

      So we have a choice between inaccurate prone-to-false-negatives rapid saliva-based antigen tests or inaccurate prone-to-false-positives PCR tests.

      What to choose…?

      Like

      1. Many thanks, Mike. You have here what is already practically an article.

        And of course, PCR is testing for a “virus” which has never been isolated and purified, testing for code created on a computer, and the antigen is testing for antibodies which are supposedly specific to this imagined virus, antibodies whose existence has in fact never been verified.

        I should mention that this person i encountered believes in a bio-weapon which is a combo of HIV and SARS. Seems to be very common among virus-pushing anti-vaxxers, i.e. they are deeply wedded to the weapon narrative, which requires a virus, and don’t wanna let go of it. When others pointed out to her that HIV is not the cause of AIDS, she responded that someone she knew got AIDS, as if this proves that HIV exists and causes it. SMH.

        Liked by 1 person

      2. Yes, sadly the HIV/SARS bioweapon narrative was a well orchestrated red herring that many fell for. It has kept them locked into the “viral” paradigm and in a state of fear. It’s too bad they do not look at the evidence for themselves.

        Like

  6. I also assumed it was a ‘bioweapon’ at first because the cutting edge of the peak oil community knew that they would mask the beginning of industrial collapse due to the world reaching peak total oil liquids production (2018/2019) with war. A good deal of the psychological sticking to a weaponized HIV-spliced virus (exosome) narrative probably has to do with the trauma separation that brian emphasizes.

    One way or the other, by hook or by crook, multidimensional war is afoot. When the farm has gotten too big for the boots of the aging Farmer, the farm must downsize just as day turns to night.

    The separation trauma of waking up in a Brave New World that makes 9/11 look like child’s play welded most minds to the clever misdirection play that was the ‘rogue’ Indian paper that was disseminated throughout both the controlled and false opposition media, and then repressed. It is the plandemic’s grassy knoll.

    And as a tool for control the separation trauma cuts both ways. Separating the mainstream babes in the wood from the placental safety of their dripfed existence, with murmurings of a biolab a mile away from a germ-infested wet market of an inscrutable oriental nature took their fear-based capture bonding to the next level, softening them up for the shots heard around the world.

    The technical counterpoint to the argument that the exosome has never been isolated is that if they’re deployed synthetic exosomes then they came into existence by isolation, by definition.

    Like

  7. Hi Mike, this may be off-topic but i was curious if you had any thoughts on the following taken from a recent Jon Rappoport comments thread. Are you familiar with blogger Jeff Green and his theory of ‘viruses’ as endogenous particles acting as toxic ‘clean-up crews’? I quote his full comment here:

    “Jeff Green says:
    May 21, 2022 at 5:33 am
    The glaring problem with this stance is those claiming viruses are not real seemingly do not have a biological understanding of why the body needs viruses to cleanse. They seem to claim, as Kaufman has, that viruses are not real because SARS-CoV-2 has not been proven to exist. That is quite the leap. They then go on to claim because this is so, that absolutely no viruses exist at all. This is not close to being the case. They base their incomplete theory on a misunderstanding of isolation itself, and what is deemed a pure isolate in the literature.

    When Kaufman and others, like Lanka, claim that viruses have never been isolated, they are mistaken. They have set in place impossible criteria to meet in order to deem a virus as completely isolated from its constituents. The literature notes an allowance of 1-2% contamination when deeming a pure isolate sample. Small amounts of contamination would naturally occur with any entity as small as a viral protein due to filtration pores and cannot be avoided without completely destroying the viral protein.

    Lanka has stated in his own writings that he himself has isolated bacteriophages, which are indeed a type of hybrid virus created by bacterium. In this way, he claims a virus exists. Since this is the case, the next logical step would be to conclude that all living cells and bacteria are able to produce their own enzymatic solvents (virus) to cleanse. All life is expressed to its ultimate climax. This is never concluded, except to say that they are merely cellular breakdowns, which is only partly true.

    At the same time, some claim exosomes take the place of viruses, yet do not seem to understand the differences between the two entities. If Kaufman claims exosomes solely engulf toxins, this is biologically impossible since exosomes are extracellular vesicles that transport fluids between cells for cellular life. Therefore, they must destroy their own fluids to take part in the dissolution of toxicity. Viruses have no such problem and are entirely designed by cells to dilute toxicity. In the end, those who make these claims have no ultimate conclusion for how the body must dissolve, dilute, and expel toxicity when large amounts of microbial and cellular life have become poisoned to death by industrial toxins. Viruses are survival mechanisms of cells during cellular breakdown.

    Another noteworthy mistake is that they believe the photos of exosomes and use them as proof, yet, they conveniently discard the electron images of viruses dating back many years to the 80s. If viruses cannot be isolated and shown to exist, neither can exosomes, for they are roughly the same size and shape, and their isolation methods and results are virtually identical.

    Since this is a limited space, you may find more information on my website by clicking my username.”

    End of Green’s quote. I feel he’s making some of the same false leaps as the virologists and immunologists in assessing what these soupy particles are doing/not doing. In fact his opening sentence is a glaring assumption declaring that ‘the body needs viruses to cleanse’. He also grossly mis-characterizes Stefan Lanka’s work discovering a type of phage from the sea which he (Lanka) at first likened to a harmless virus before later clarifying his understanding of these small, bacterial organisms. In fact, Lanka states that he would not use the term ‘virus’ anymore unless referring to its latin etymology as a toxin or poison.

    Any thoughts are gratefully welcome.

    -Keith

    Liked by 1 person

    1. I completely agree that he is making assumptions and leaps right off the bat. He is assigning form and function to particles seen in EM that are themelves assigned to fictional entities that existed as ideas first. Oddly enough, he is spot on when he states that exosomes and “viruses” can not be shown to exist as neither can be properly purified and isolated nor seen in a living state. He is stuck in a conceptual framework on how he believes the body is supposed to work and function while ignoring that this is all theoretical and has never been proven according to adherence to the scientific method. He would understand this if he traced every belief back to the original source for where that particular belief was created.

      Like

    2. Green’s views on virology seem not to be well sussed out.

      – He uses semantics to try to argue that “viruses” exist when he really means essentially cell soap (cf. TC Fry, Aajonus Vonderplanitz, and others, not sure who is the originator of this idea). Such solvents may exist and be important, but they aren’t what virologists and most of the rest of the world are claiming exists and spreads. He seems to want to borrow some of the mainstream legit-sounding-ness while rejecting it at the same time, by piggybacking on their phrasing.

      – He’s about two years behind on the arguments. Kaufman and most others questioning virology no longer try to claim it’s really just “exosomes,” as the reality is what they point-and-declare to be “viruses” run the gamut of cellular breakdown products. They refer to no one object. The exosome idea was only something Kaufman threw out as a very early conjecture in a video or two that happened to blow up.

      – Green hasn’t even made a token effort kept up on the arguments if he thinks Kaufman and other headline “virus” skeptics have only looked at foundational evidence for one “virus.”

      – He takes Lanka’s point that bacteriophages exist and are isolate-able in a purified manner (so why shouldn’t other “viruses” be?) and uses semantics to try to say that proves “viruses” can be isolated. He misses the point that virologists call a bunch of things “virus” but all the so-called pathogenic ones have never been shown to exist. The argument is about the existence of pathogenic things they call “viruses.” Not any old thing they call “viruses”! Talk about being out of touch with the state of the debate; not a good look for an alternative thinker in this field, in my opinion.

      – On 1-2% contamination, is he claiming we have 98-99% pure soups of “virus” particles? I haven’t seen nor heard of anything remotely like that even being claimed let alone verified.

      Overall his attitude strikes me as a cautionary tale about sticking to one’s own cloistered world and not jumping into debate from time to time with a broad audience as a reality check.

      Liked by 2 people

      1. Thanks Mike and ClariFire! You put words to what was brewing in my mind. I remember Kaufman’s exosome reference from a long-format interview he did with Brian Rose (an early source for covid dissidents) around May 2020. Dr. Cowan also refers to a peer reviewed paper (citation missing) that finds that they cannot distinguish between “viruses” and exosomes as they are of similar size and morphology. He uses it not to hypothesize on the existence of either but rather to show the muddled mess of “point-and-declare” (to borrow one of Mike’s favorites) guesswork in virology. And you’re right, Green seems to be latched onto a pet theory of “viruses” and their function while those of us in the virus-as-hoax arena are able to adapt and move on from prior readings.

        All this reminds me of the great theological debates of the early Christian mystics. Two camps materialized: one applying a ‘cataphatic’ approach to determining the nature of ‘God’ (quotes are mine) by enumerating his/her/its various attributes, powers, purview, etc. That is, WHAT EXACTLY is it. A bit presumptuous but nonetheless (virus true believers…). The others pressed for an ‘apophatic’ rendering of their cherished deity. That is, description by remotion: a long litany of what ‘God’ most certainly IS NOT. They were content to leave room for the mystery, the unknown, also summed up in the Sanskrit saying ‘neti-neti’ or ‘not this, not that’. Seems we virus debunkers are the apophatic iconoclasts of virology and its fanatical devotees.

        Liked by 1 person

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