HIV/AIDS Skepticism

Pointing to evidence that HIV is not the necessary and sufficient cause of AIDS

Dr. Frankenstein turns to CCR5

Posted by Henry Bauer on 2008/07/31

It was once imagined that Europeans are protected from “HIV” by the CCR5Δ32 gene (CCR5 with deletion 32). However, comparison of the geographic distributions of CCR5Δ32 and of “HIV” disproves that suggestion [Mainstream duffers clutch at Duffy straws: African ancestry and HIV, 26 July 2008]. No sooner had we posted that information than HIV/AIDS “researchers” publish a brilliant scheme for mimicking the  Δ32 deletion via genetic engineering, as “an attractive approach for the treatment of HIV-1 infection”:

“Homozygosity for the naturally occurring 32 deletion in the HIV co-receptor CCR5 confers resistance to HIV-1 infection. We generated an HIV-resistant genotype de novo using engineered zinc-finger nucleases (ZFNs) to disrupt endogenous CCR5. Transient expression of CCR5 ZFNs permanently and specifically disrupted 50% of CCR5 alleles in a pool of primary human CD4+ T cells. Genetic disruption of CCR5 provided robust, stable and heritable protection against HIV-1 infection in vitro and in vivo . . . . HIV-1-infected mice engrafted with ZFN-modified CD4+ T cells had lower viral loads and higher CD4+ T-cell counts than mice engrafted with wild-type CD4+ T cells, consistent with the potential to reconstitute immune function in individuals with HIV/AIDS by maintenance of an HIV-resistant CD4+ T-cell population. Thus adoptive transfer of ex vivo expanded CCR5 ZFN–modified autologous CD4+ T cells in HIV patients is an attractive approach for the treatment of HIV-1 infection” (Perez et al. [23 authors, correspondence to C. H. June], “Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases”, Nature Biotechnology 26 [2008] 808-16).

This brings out in force the Luddite that has been growing in me, fertilized by the copious manure that emanates non-stop from the drug industry and its academic henchpeople. (Luddites are named after the machine-destroying protesters in 19th-century Birmingham whose jobs were lost to mechanization during the Industrial Revolution. It’s come to be applied to antagonism against things that are widely applauded as scientific or technological “improvements” or “advances”.)

There are at least two immediately obvious things very wrong with this sort of anti-HIV approach, irrespective whether HIV has anything to do with AIDS. First, gene therapy remains an idea, not a reality—moreover, an idea whose time has passed because its basis has been found to be incorrect. Second, does not the CCR5 gene perform any functions apart from its possible connection to “HIV”? What are those functions? What happens to them if CCR5 is disrupted in a manner that natural selection (or the Creator, makes no difference) never invented or intended?

The idea of gene therapy stemmed from the initial interpretations of DNA as the carrier of hereditary information. It was thought at first that specific sequences of DNA form distinct and separate genes, individual units of hereditary information, each of them responsible only for the production of one particular protein. That has turned out to be not the case. Genomes are dynamic systems and not linear arrays of fixed genes. At various times, different sub-units of what are still called “genes” work together with sub-units of other “genes” to generate the proteins needed at any given time and place. The sophistication of these precisely scheduled interactions is such that genomes can produce many more proteins than they have “genes”: humans have fewer “genes” than corn and only 25% more than flatworms, even though humans are somewhat more complex creatures; see the fairly recent review by Ast, “The alternative genome”, Scientific American, April 2005, 58-65.

Given that current understanding, any notion of replacing a “defective gene” with a non-defective one presupposes that we know everything about which bits of which genes are needed for what, and at which times, in the development and life of the organism. Our knowledge is very far from that.

Official websites describe the problems quite well:

“Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently only being tested for the treatment of diseases that have no other cures” [published 18 July 2008]

“The Food and Drug Administration (FDA) has not yet approved any human gene therapy . . . . Current gene therapy is experimental and has not proven very successful in clinical trials. Little progress has been made since the first gene therapy clinical trial began in 1990. In 1999, gene therapy suffered a major setback with the death of 18-year-old Jesse Gelsinger. . . . [who] died from multiple organ failures 4 days after starting the treatment. . . .  Another major blow came in January 2003, when the FDA placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells. . . .  after . . . a second child treated in a French gene therapy trial had developed a leukemia-like condition. . . . Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problems with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long-term benefits. Patients will have to undergo multiple rounds of gene therapy. . . . Anytime a foreign object is introduced into human tissues, the immune system is designed to attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a potential risk. Furthermore, the immune system’s enhanced response to invaders it has seen before makes it difficult for gene therapy to be repeated in patients. . . . Viruses, while the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient—toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease. . . . Conditions or disorders that arise from mutations in a single gene are the best candidates for gene therapy. Unfortunately, some the most commonly occurring disorders, such as heart disease, high blood pressure, Alzheimer’s disease, arthritis, and diabetes, are caused by the combined effects of variations in many genes. Multigene or multifactorial disorders such as these would be especially difficult to treat effectively using gene therapy. . . .” [last modified 13  May].

Perez et al. ingeniously avoided some of those problems, but the basic lack of knowledge remains. The disruption of CCR5 also disrupted the genome at other sites, chiefly at the neighboring CCR2: “Loss of CCR2 in CD4+ T cells is predicted to be well tolerated as CCR2-/- mice display phenotypes that are not disabling . . . . Mutant alleles of CCR2 have been correlated with delayed progression to AIDS in HIV-infected individuals, although no influence on the incidence of HIV-1 infection was observed . . . . Thus, parallel mutation of a small proportion of CCR2 in CD4+ T cells ex vivo is unlikely to be deleterious . . . . ”; and there was also disruption at “an intron of ABLIM2 on chromosome 4”. “Thus, except for CCR2 (5.39%), and rare (~1/20,000) events at ABLIM2, all the remaining sites showed no evidence of . . . [disruption], given a threshold level of detection of ~1 in 10,000 sequences”.

In other words, the engineering of the CCR5 gene is not 100% specific, other parts of the genome are affected. That no deleterious “side”-effects were observed in the experimental mice is hardly persuasive that the procedure could do in human beings only the one thing we want done and nothing else. Above all, Perez et al. say nothing about why CCR5 exists at all, what functions natural selection intended for it, and whether the CCR5Δ32 that supposedly protects against “HIV”—but doesn’t, according to epidemiological comparisons—is associated with any undesirable conditions.

So, I suggest, Perez et al. are tinkering with things they don’t understand and that are better left alone, hence my reference to Dr. Frankenstein. Incidentally: if you think “Frankenstein” was written by Mary Wollstonecraft Shelley, you should read John Lauritsen’s “The Man Who Wrote Frankenstein”, an illustration that it’s not only in medical science that the mainstream consensus can be wrong for long periods of time. The dogma that the Clovis people were the first Americans was maintained for more than half-a-century in the face of contradicting evidence as well as the implausibility of the idea that the earliest discovered habitation sites would correspond with the earliest actual sites. Back to literary scholarship: it is also not the case that William Shakspere of Stratford-on-Avon wrote Shakespeare’s works, see Diana Price, “Shakespeare’s Unorthodox Biography: New Evidence of an Authorship Problem” ).

4 Responses to “Dr. Frankenstein turns to CCR5”

  1. Martin said

    Hi Dr. Bauer, The only criticism I have of your very erudite disassembling of the CCR5 stuff, is that you take it seriously enough as though it were scientific. But I may be missing your point in that you are doing this as sophisticated humor. The research you criticize is used to bamboozle AIDS Establishment Accolytes to contribute more money because they just spent it all on (worthless) studies like the CCR5 one. I guess we dissidents are caught between a rock and a hard place when trying to criticize the AIDS Establishment and the so-called science and medicine that it pushes. It’s really academic when we criticize such stuff. It’s like criticizing the hypothesis of a sophisticated statistical study on a complex 3D matrix of how Angels would stack up on the head of a pin or calculating the size of an Angel that in large numbers could be stacked on the head of a pin. One first has to believe in Angels.
    I saw a very funny “study” in a journal of improbable science about after very many twirls of a dreidl the statistical analysis showed that God was left handed.

    By the way, I have read John’s book “The Man Who Wrote Frankenstein”. It’s funny about Celia Farber getting the Semmelweiss award because John Lauritsen wrote on the subject way before Farber did. He should have been named.

  2. Henry Bauer said

    Martin, yes, it’s difficult to critique the HIV/AIDS stuff without seeming to take its substance seriously. But I’ve found that by following their trails and looking at relevant data sometimes brings rewards, as when I couldn’t believe Sharon Stone’s parroting of AIDS death figures and, looking at the source data, found clear evidence that (1) antiretrovirals haven’t extended life and (2) there’s no latent period after “HIV infection”—“HIV DISEASE” IS NOT AN ILLNESS, 19 March 2008, https://hivskeptic.wordpress.com/2008/03/19/“hiv-disease”-is-not-an-illness/

    John Lauritsen: Yes indeed, if anyone deserves to be recognized for insight and dissent from the very beginning, it is John Lauritsen. He was right about poppers, he was right about AIDS and what the real risks are, he pointed out how misleading the CDC’s classification scheme was. Not to take anything away from Celia Farber’s long and honorable journalism, or from a number of other writers and rethinkers, but John was there FIRST on several central matters, and it’s much harder to see something correctly when no one else yet has. I respect him enormously, and have learned much from his writings, not least from his jointly authored “The Early Homosexual Rights Movement”.

  3. Dave James said

    While applicable to the older technology, your arguments do not apply to the new CCR5del++ (SB728) therapy for HIV:

    Gene therapy has already been proven to work: a number patients with SCIDS (severe combined immune deficiency syndrome) have been cured by it already. The treatment had to be discontinued becuause a few of them got leukemia due to the vector used to accomplish the genetic changes. 1) other than that, it did cure the disorder: the rest of the treated patients are now leading completely normal lives despite what would have otherwise been an invariably fatal condition 2) there is a newer method now available that does not use vectors and will be able to accomplish exactly the same gene change but without causing leukemia in some patients because it does not (in it’s latest version) use a vector for delivery.

    I’m not sure what you mean by “its basis has been found to be incorrect” but that simply is not true. Every technology goes thru a process of development and early stages always have problems. That in no way means that their basis is incorrect: it often just means that further development is required.

    Note that there are many genetic diseases in which the mutation/variation that causes the disease is clearly detrimental: it always causes a serious problem when present. Many people who DON’t have it are very healthy so obviously it’s not required. That’s true regardless of how many additional pathways it may or may not affect.

    “Second, does not the CCR5 gene perform any functions apart from its possible connection to “HIV”” If the CCR5del (deletion) causes any problems they cannot be more than minor (when present in one copy). We know that this is true because the gene is present in a high percentage of the population (about 10%). There are some genes that when present in such percentages confer a strong positive benefit when present in one copy (heterozygous) but cause serious problems when present in two copies (homozygous). THis is a “trade off”: the number of those with two copies is far less than those with only one copy (for 10% level, about 1/20 as many) which is why the gene is not “selected out” of the : one copy gives resistance to malaria, two copies make your life H—. A gene that causes serious problems when present in only one copy is simply not going to be able to increase to that high a percentage of the population.

    What we know is that many CCR5del++ people are very healthy and lead normal lives. Far more relevant is that new therapy (SB728) does not change ALL the cells in your body: just some of the immune cells. All other cells will continue to produce the CCR5 (cell surface receptor) . So the treatment can’t make you any worse (because the HIV was going to kill your immune cells anyway, so in any case you’d be left with no immune cells that produce CCR5 (a type of cell surface receptor) Better to have immune cells that are CCR5del++ than no immune cells at all! And all the other cell are still CCR5++ (no deletions)

    “the engineering of the CCR5 gene is not 100% specific, other parts of the genome are affected”

    This is totally inapplicable to the NEW (SB728)therapy: the zinc finger technology used, in stark contrast to all previous methods of genetic modification, makes exact genetic modifications to exactly the location intended and to no other location. Current versions to use a vector delivery. However there is a new version under development that has been shown to work with no vector whatsoever and it will have none of the problems associated with them.

    Gene therapy is no longer what it used to be. Zinc finger technology can add, delete, edit, up regulate or down regulate any gene in any organism and, if desired, only in whatever specific tissue is intended and not in the rest the organism. W

    it should be noted that, as per the above example, many if not most genes are not inherently beneficial or detrimental: it’s a question of trade-offs, what other genes are present in the individual, what environmental influences the individual is subject to, what the diet is, and many other factors. Inappropriate simplification can lead to some very wrong conclusions.

    All that being said, I very strongly agree with your indications that the overall situation is far more complex and interconnected than many people appreciate. Because of that a great deal of caution is appropriate. The current approach being used in the SP 728 (CCR5del++ therapy) is appropriately cautious and consists at present of modifying cells outside the body and then returning them. This is an inherently incapable thus the changes are inherently incapable of being passed on to subsequent generations. In addition only a particular cell type is being affected. Since they are extracted from the body and genetically modified outside of it is inherently impossible that any other body cells could be affected by the genetic modification inadvertently genetically modified.

    As is often the case with medicine. Advancement will consist of a series of very small incremental steps an initial uses will be impatience with very serious conditions (like HIV) whose conditions are considered to warrant some degree of risk for the development of therapies.

    All things change. Your arguments were applicable (in some cases) to the old therapies but will not apply to at least one of the new ones.

    • Henry Bauer said

      Dave James:
      Let’s see how well or badly this stands up in the next years. So many breakthroughs turn out not to be.

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