Sunday, November 6, 2011

TIME FOR A HOUSECLEANING AT NIH

The following manuscript was submitted to (and rejected by) the New Enron Journal of Medicine.

Abstract: The HIV Vaccination Program needs to be reappraised in light of continuing failures and the published experiments on HIV-1.

The Wrong Road Has Been a Long Road

In [13], Dr Fauci and co-author make the penultimate statement: “the body is indeed capable of producing potent, broadly neutralizing antibodies (against HIV); however, it does not do so readily or efficiently”. Such a bold statement on this one particular retrovirus requires absolute physiological back up. The problem is that NIH has never provided such information for the benefit of taxpaying public.

And such a broad brush, presumably applicable to billions of people, begs the question: which body?

Based on many immunosuppressive agents, as documented by Root-Bernstein [15] for environmental stressors that compromise optimum immune system function, one would expect a wide variance among individuals in this capacity. This includes a negative, not a protective effect, known as antibody dependent enhancement documented for RNA enveloped viruses like dengue virus infection. [16]

And Dr Fauci should be hauled into Congress to explain why there are “T cells that effectively control cytomegalovirus, a common chronic viral infection”[18], since CMV has roughly twenty-fold the genomic size of HIV-1 and reasonably should have a far greater capacity to “use tricks” or “escape from” immune surveillance.

Failure to recognize simple facts and their connection to previous failed attempts at an HIV vaccine means NIH conventional HIV/AIDS Vaccine Research should be scrapped as a waste of taxpayer’s money. Those responsible for this boondoggle should be fired.

Dr Fauci has maintained the false belief that HIV is an organism subject to the law of evolution. If the virus really was an autonomous organism-like agent that “evades and undermines the immune system”, replicons of its complete dimeric genomic would be detectable in patients so affected.

Inadequate explanations by the NIH for this failure to find the required evidence - whole virus in AIDS patients - for the past 30 years requires public scrutiny and a new team. Congress should bring their budget slashing approach to the HIV Vaccine Program where failure is always rationalized as success.

It’s 27 years since Dr Gallo’s claim of “continuous production” of HIV particles from his special cell culture [1] and Secretary Heckler’s Press Conference in early 1984 where a vaccine was promised in a few years.

Since this initial failure, the program has been maintained with whatever rationalizations are handy as HIV experts scramble for reasons why numerous HIV vaccine program failures have “plunged the effort into disarray”.[6] “(E)very failure has revealed tricks this virus uses, suggesting new ways to go after it.”[6] But it is an absolute nonsense that a virus, being nothing more than nucleic acids with a protein/membrane coating, can use “tricks”, or “mutate itself” in such a way as to escape immune surveillance.

A Retrovirus from Krypton?

For example, it is said that: “When HIV-1 infects a permissive cell, integration occurs within a genomic context of endogenous retroviruses. In HIV-1-infected cells, the virus initiates numerous changes in the cellular environment to enhance its own expression, which also affect the endogenous retroviruses in the genome. Intracellular defense mechanisms are compromised by proteins like Vif, which works against cellular APOBEC proteins, helping to establish a productive HIV replication.”[18]

Now obviously, a mutation that prevents translation of Vif means the intracellular defensive system will block HIV infection.

So Dr. Fauci’s contradictory claims that “unnatural immunity” is essential for a “prevention toolkit” to end the global AIDS pandemic require this rebuttal. Of course, it’s not entirely his fault given the inbred research community that’s grown up around the HIV/AIDS problem. Dr Fauci, flying in the face of Dr. Montagnier’s comments that natural immunity can prevent or control HIV infection [14]; and as demonstrated in fact by “long term non-progressors”, confusingly combines the natural and synthetic. "Where effective vaccines have been developed, such as smallpox, measles, and poliovirus, there exists a natural model of protection: the immune response to the pathogen ultimately clears the microbe from the body and confers durable protection against reinfection.”[13] However, measles vaccinations apparently require “booster shots” given measles epidemics in vaccinated populations, which calls into question his idea of “effective” and “durable protection”.

But what counts with any infection is not a vaccine that just pumps up the quantity of antibodies, it’s a balanced immune response including a diverse repertoire of T-cells that will be produced within the healthy.[2] This was documented originally by Edward Kass even before subpopulations of lymphocytes were recognized, “the decline in rates of certain disorders, correlated roughly with improving socioeconomic circumstances, is merely the most important happening in the history of the health of man.”[3, pg 111] And: “It is important that this point be understood in its completeness…Our research efforts in dealing with (measles) …do not account for the linear decline in deaths during the past 100 years.”[3, pg 111] Figure 5 shows the “mean annual death rate from measles” in 1890 as roughly 1200 per million declining to <50 per million when the “virus” was “identified” in 1955.[3, pg 112]

Is Reverse Transcription a Natural Function of Polymerase Enzymes in Stressed Cells?

Furthermore, it is simply assumed that injection of crude virus preparations of the smallpox and polio vaccine eras were able to clear the viral agent from the body. Unknown at the time was the cell’s ability to “archive”, via endogenous reverse transcription, the genomes of RNA viruses like measles and polio within the nucleus. This is biochemically equivalent to the “persistence” of HIV infection as a so-called proviral form in the cell’s nucleus and paradoxically, may represent a protective effect. [4]

It was biochemically proven for poliovirus by Spiegelman’s group in 1977 that polymerase enzyme for reverse transcription need not be specific to retroviral RNA template. (Just as the enzyme can transcribe a DNA template.) “We have recently reported that purified reverse transcriptase … of the avian myeloblastosis virus (AMV) can mediate the synthesis in high yield of virtually complete DNA complementary copies of poliovirus RNA.”[5]

Could such a “natural DNA vaccine” shift from protective to pathogenic and produce the HIV markers? An alternate exlanation for “immunodominant epitopes” leading to AIDS is in order if lymphocytes and monocytes are overloaded with latent viral infections. According to Nobel Laureate Kary Mullis, “the cells of an individual immune system could be so highly infected with latent viruses that were immunologically distinct from one another as to result in an immune dysfunction resembling the Acquired Immune Deficiency Syndrome”. [9, Abstract] Clearly if this is the case in AIDS, attempts at vaccinating against a single agent are doomed to fail.


Return on Investment + Demand for Instant Explanations = Foot-in-the-Mouth Science


Dr Fauci and co-author state: “We have known since the mid-1980s that the body's natural immune response to HIV infection is completely inadequate. A ‘natural’ immune response that might adequately control HIV infection does not occur at all, occurs too rarely, is too weak, or is too slow to begin.” But why should this be the case in one particular retrovirus, “behaving” as no other?* Somehow it is supposed to take over a cell even when there’s no in vivo evidence for its presence in such quantities that would demonstrate this.

Are these “instant explanations” [7, pg 139-140] of non-living entities, “intellectual lethargy” on the part of molecular biologists, a “caricature of Darwinism” where “adaptive value” is the magic potion to make acceptable the idea that “HIV causes AIDS” is a confirmed hypothesis without adequate “functional or mechanistic explanations” of this putative etiological pathway?

Instead of an etiological explanation, considering the known biochemistry, Dr Fauci rests his case on “mathematical biology”.


Garbage In Garbage Out


According to leading authorities in field: “Two assumptions are central to the theory: (1) mutation via reverse transcription during viral replication can generate viral strains resistant to neutralization by antibodies specific to earlier mutants in a particular host; (2) the virus can kill the CD4-positive lymphocytes that play a role in mounting an immunological attack directed at the virus.” [8]

But many experiments on HIV-1 provide no validation of this model. According to published results, the consequence of genomic mutations is a defective virus with no ability to replicate. [11, 12]

Nowak et al may be perpetuating the fallacy of “hyperevolutionism”, as explained by Stent (pg 139): “(T)here are nevertheless some intellectually noxious consequences of evolutionism, or rather hyperevolutionism, which have become manifest in our days. And the resurgence of Scientific Creationism will have done professional biologists a good turn if it causes them to reflect on these consequences. The responsibility for current excessive claims on behalf of evolutionism does not so much lie with the leading architects of modern evolutionary thought who, from Darwin onward, were generally aware of the epistemological status of their work, but with the epigones who failed to comprehend the intrinsic limitations of the theory. First, it would appear that the idea of natural selection as the grandest of all biological principles – a unifying “law” to which all explanations must ultimately refer – has been carried too far. Apparently it has been widely forgotten … that natural selection is foremost a diachronic or historical principle whose main explanatory value concerns biological processes that occur over periods of time that are long with respect to the life span of the individual organism, i.e. evolutionary phenomena. By contrast, natural selection has little or no standing as a synchronic principle that can be drawn on for explanations of biological processes that occur over periods of time that are short with respect to life spans, i.e. physiological phenomena.” He goes on to criticize teaching students that “‘adaptive value’ will explain everything.” [7]

Many examples illustrating Stent’s point come from the world of animal eukaryotic parasites. They take on different forms (morphology and function appropriate to the specific host) that can be explained via physiological principles. They don’t “adapt” in an evolutionary sense in their dealings with animal immune systems, they change their form [17]

Even if we don’t agree with Stent, an entity should be capable of at least replicating its own genome via a complete thermodynamic work cycle if it’s to evolve. (19) If this is not in evidence, and it seems to be the case with viruses, the data from HIV cell culture experiments should be interpreted physiologically “without the grandest of all biological principles”. Given full length endogenous retrovirus-like elements (RLE), constituting 1% human genome, and some with open reading frames (20); polymorphisms within human population of RLE can account for different “HIV strains” extracted as “primary isolates”. (21)

So when looking at the accuracy of such metaphors as “evolving” and “life cycle” in describing retroviruses there’s no “historical principle” or completion of a “thermodynamic work cycle”. (22,19) How can viruses be subject to natural selection when they are fixed as non-autonomous components of living eukaryotic cells or crystals when outside of organisms? Of course there are “special properties” deserving investigation. And they cut both ways – cell-killing (which can be protective, e.g. cancer cell) and cell resurrection. (10).

Conclusions

1. Unreal metaphor of species cannot be applied to entities that are not alive in the first place. Presumably the “quasi” in quasispecies conveys the “epistemological awareness” of the authors, but it is more likely an example of “hyperevolutionism” to say that viruses “adapt” to the immune system, or “evade it” based on mutations that most likely simply prevent replication (defective virus).

2. “(C)oevolution and coexistence of many (HIV) viral mutants in one infected person” can have an alternate explanation. Since there’s no “co-evolution”, only physiology, consideration of multiple latent viral infections in AIDS is called for in terms of potential vaccines.(9) The never validated math model of “an increasing number of antigenically distinct (HIV) viral strains (that) may overwhelm the immune system of the host” [8], should be reappraised considering the Mullis and Root-Bernstein models. And Dr Fauci, hopefully, will gracefully retire to make way for new views - necessary after decades of failure.

3. According to the first immunodominant epitope assumption of Nowak et al [8], it appears we have a case of Stent’s “hyperevolutionism”. If retroviruses are not organelles constrained by the cellular environment, the extraction of complete RNA dimeric genomes ex vivo (spinning to the 70S band) would be possible. This would be evidence for HIV’s alleged immunodominance in vivo, a quantity (10^10 genomes/ml = 200ng/ml) directly from patients. But since such an isolation directly from patients of HIV-1’s complete genome has never been reported, it’s likely that attempting this measurement has resulted in null experiments. Apparently, there’s no incentive in present NIH structure to maintain funding if a research group publishes such experiments.

*HERVs are “dead” or “inert”[18], but somehow HIV, with major genes biochemically equivalent, is very much alive.

References
1. Popovic ... Gallo et al; Detection, Isolation and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS. Science V224, (4 May 1984), pg 499

2. Pantaleo et al; The qualitative nature of the primary immune response to HIV infection is a prognosticator of disease progression independent of the initial level of plasma viremia. PNAS, (January 7, 1997) vol. 94, 254-258. “This study reveals that the primary immune response to HIV is qualitatively different among individuals. It is highly likely that both host and virologic factors contribute to the generation of this diversity.” So healthy people don’t get sick from HIV. “Both vigorous humoral and cellular immune responses have been detected during primary infection, and the temporal relationship between the appearance of an HIV-specific immune response, down-regulation of viremia, and resolution of the acute viral syndrome has been clearly established.”

3. E.H. Kass; Infectious Diseases and Social Change. Journal of Infectious Diseases, (January 1971), V123, 110 – 114)

4. Klenerman et al; A Non-retroviral RNA Virus Persists in DNA Form. Nature, (20 November 1997) V390, 298-301. “These findings reveal a surprising and new pathway of interaction between exogenous RNA viruses and endogenous retroviral, and perhaps other host components, that results in the persistence of virally determined DNA.” And: “It may also be relevant for human persistent RNA viruses such as hepatitis C virus and measles.” The authors speculate on a novel form of acquired immunity: “The ability of antigen presenting cells such as macrophages and B cells to accumulate viral DNA genome thus potentially represents a naturally produced form of DNA vaccine. In this context, even low levels of major histocompatibility (MHC) peptide complexes on a few cells in lymphoid organs may be immunologically important. The mechanisms involved in the maintenance of immunological memory may be multiple, but persistence of viral template in stable DNA form may contribute to this.”

5. Myers et al; PNAS, (July 1977) V74, 2840-2843

6. David I Watkins; The Vaccine Search Goes On. Scientific American, November 2008, 69-76

7. Gunther Stent, in Montagu, ed; Science and Creationism (1984), Oxford University Press, pg 136

8. Nowak, Martin A.; May, Robert M.; Anderson, Roy M.; The evolutionary dynamics of HIV-1 quasispecies and the development of immunodeficiency disease. AIDS. 4(11):1095-1104, November 1990

9. Mullis, K; A hypothetical disease of the immune system that may bear some relation to the Acquired Immune Deficiency Syndrome. Genetica 95: 195-197, 1995.

10. Villareal, L; Are viruses alive? Scientific American, December 2004

11. R J Gorelick, S M Nigida Jr, J W Bess Jr, L O Arthur, L E Henderson, and A Rein; Noninfectious human immunodeficiency virus type 1 mutants deficient in genomic RNA. J Virol. 1990 July; 64(7): 3207-3211

12. Tang et al; Human Immunodeficiency Virus Type 1 N-Terminal Capsid Mutants That Exhibit Aberrant Core Morphology and Are Blocked in Initiation of Reverse Transcription in Infected Cells. Journal of Virology, October 2001, p. 9357-9366, Vol. 75, No. 19

13. Margaret I. Johnston, Anthony S. Fauci; N Engl J Med 2011; 365:873-875, September 8, 2011

14. B. Leung Interview of L Montagnier; HIV Can Be Cleared Naturally - House of Numbers. http://www.youtube.com/watch?v=tKyIBYKoT20 (accessed 10/8/11)

BL: Is treating oxidative stress one of the best ways to deal with the African AIDS epidemic?

LM: I think this is one way to approach, to decrease the rate of transmission because I believe HIV, we can be exposed to HIV many times without being chronically infected, our immune system will get rid of the virus within a few weeks, if you have a good immune system; and this is also the problem of African people. Their nutrition is not very equilibrated, they are in oxidative stress, even if they are not infected with HIV; so their immune system doesn’t work well already. So it is prone, it can, you know, allow HIV to get in and persist. So there are many ways, which are not the vaccine, the magic name, the vaccine, many ways to decrease the transmission just by simple measures of nutrition, giving antioxidants – hygiene measures, fighting the other infections. So they are not spectacular, but they could, you know, decrease very well the epidemic to the level they are in occidental countries, western countries.

15. R.S. Root-Bernstein; NON-HIV IMMUNOSUPPRESSIVE FACTORS IN AIDS A: MULTIFACTORIAL, SYNERGISTIC THEORY OF AIDS AETIOLOGY. Res. Immunol. 1990, 141, 815-838

16. R Anderson, S Wang, C Osiowy, and AC Issekutz; Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes. J. Virol., Jun 1997; 71: 4226 - 4232.

17. S Baron (ed); Medical Microbiology (1986), Addison Wesley Publishing Company

18. Garrison et al; T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection. PLoS Pathogens 2007;3(11). (accessed 10/10/11)
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0030165

19. Stuart Kaufmann; Investigations. Chapter 3: Autonomous Agents, 49 (2000), Oxford University Press. “An autonomous agent must be an autocatalytic system able to reproduce and able to perform one or more thermodynamic work cycles.”

20. Villesen et al; Identification of endogenous retroviral reading frames in the human genome. Retrovirolgy. 2004 Oct 11;1(1):32

21. Gallo et al; Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk from AIDS. Science V224, (4 May 1984), 500-503

22. Stephen J. Gould, Amy M. Booth, James E. K. Hildreth; The Trojan exosome hypothesis. PNAS, 2003 100 (19) 10592-10597

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