Genomic Variability 14 October 2003
Previous Rapid Response Next Rapid Response Top
Eleni Papadopulos-Eleopulos,
Biophysicist
Department of Medical Engineering and Physics, Royal Perth Hospital, Western Australia 6847,
Valendar F. Turner, John Papadimitriou, Barry A. P. Page, David A. Causer, Helman Alfonso

Send response to journal:
Re: Genomic Variability

In his rapid response "Re: Re: Re: Re: A critical examination of the evidence for the existence of HIV" (22 September 2003), Christopher Noble wrote: "The nature of the scientific misconduct that Christopher Tyler refers to is also alluded to by Gallo: " In fact, our IIIB isolate was accidentally contaminated with a sample sent to us by Montagnier."

I will not judge how accidental or knowlegable this contamination was but will focus rather on how it is now known that this contamination occured. In fact, it is from genetic sequencing of these isolates that we have evidence of the contamination."

Since: (i) for "HIV" infectivity gp120, that is, the knobs, spikes on the particles is said to be absolutely necessary (1, 2, 3); (ii) Montagnier sent to Gallo cell-free material (supernatant); (iii) cell-free particles do not have knobs, that is, gp120 (4);

it is not possible for Montagnier’s "HIV" to have contaminated Gallo’s culture. So the reported "genetic sequencing" findings will have to be explained by some other way.

Christopher Noble wrote: "It is indeed ironic that so-called dissidents are so keen on discrediting genetic sequencing studies as evidence of the existence of HIV but are so ready to jump on studies using the same techniques to demonstrate that two HIV isolates are essentially the same strain and originated from the same source. The so-called dissidents want to have their cake and eat it too. They want to claim that Gallo stole Montagnier's HIV and at the same time claim that HIV does not exist."

Let’s make it clear, we have never stated that "HIV" does not exist, but that the presently available evidence does not prove its existence. Also we have never claimed that "Gallo stole Montagnier’s HIV". In fact, as we have just stated above, this would have been an impossibility even if one assumes that there is proof for the existence of "HIV".

Christopher Noble wrote: "If PCR amplification is totally non-specific or if the sequences that are amplified are just endogenous retroviruses, as the Perth Group likes to claim, then there can be no evidence that Gallo's and Montagnier's isolates were identical, or that Gallo stole Montagnier's isolate, or that he covered anything up."

Since it is not possible that "Gallo stole Montagnier’s isolate", then it is not possible that "Gallo’s and Montagnier’s isolates were identical".

In his rapid response "Re: Finding wood among the trees" (23 September 2003), Christopher Noble wrote: "The Perth group have been making the same claim since at least 1998."By comparison, two RNA containing viruses (polio and influenza, the latter after 27 years of dormancy,) vary by less than 1%"

I have previously provided the citation for this quote. It is taken from the Perth Group presentation at the Geneva AIDS conference (satellite meeting). (1)

You have made a specific claim about the genomes of both the polio virus and the influenza virus. You have directly compared the genetic variation in these two viruses with that in HIV. You have used this comparison to formulate an argument against the existence of HIV. You have used this claim not once but many times (2-5).

Now after I have provided you with references showing that poliovirus and influenza A isolates vary by much more than 1% all of a sudden you are no longer interested in these viruses. Why?

I have provided you with the sequences for the three Sabin poliovirus vaccine types. Why do you refuse to look at them? I asked you a simple direct question. Why do you refuse to answer it?

Two types of influenza A are currently cocirculating; H3N2 and H1N1. I have provided you with sequences from the same year from these two influenza viruses. The sequences differ by approximately 50%. Why do you refuse to look at these sequences? Why do you refuse to answer simple questions?"

Suppose for the sake of argument that there are published papers with evidence (and not merely evidence in databases) which prove that in RNA viruses the nucleic acid "sequences differ by approximately 50%" and that the viruses "differ from each other by 81% at the amino acid level". We have stated that the variability of the "HIV" genome was considered as a minor point against the claimed proof for its existence. It was introduced only in regard to the issues of defining "HIV" infection in molecular terms, by antibody testing, protein function and design of vaccines, which with the exception of antibody testing, Christopher Noble has not addressed. The questions surrounding the existence of "HIV" are basic scientific questions which Christopher Noble refuses to address.

Christopher Noble wrote: "You have previously asked me a question "how it is possible with such variability to have proteins which have the same function, to induce the same antibodies which can be detected with a single antibody test, and to define "HIV" infection in molecular terms?" Contrary to you assertion I have answered this question. There is not a single antibody test but a multitude of them. The initial antibody tests were based on viral lysates isolated from a small number of AIDS patients. Since then antibody tests have incorporated recombinant proteins, synthetic peptides or a combination of the three. Originally the antibody tests that are approved by the FDA were based only on HIV-1 group M. Since then antigens specific to HIV-2, HIV-1 group O and other non group M virus types have been added precisely because these tests were failing to detect non HIV-1 group M viruses.(6)"

Christopher Noble has never answered our questions regarding protein functions and the identification of "HIV" infection in molecular terms or design of vaccines. His reference 6 is the web address for these rapid responses but there Christopher Noble did not give any references apart from a reference to the Vironostika test kit. The Vironostika test is an ELISA test which is considered to be not sufficient to prove "HIV" infection in developed countries.

Christopher Noble wrote: "The Vironostika HIV Uni-Form II is one of the antibody tests that includes HIV-1 group O specific antigens.(7) It is not an exception as you claim it is one of many tests that incorporate HIV-1 group O specific antigens."

Where are the other tests? As far as Vironostika is concerned, here is the answer to our questions from Biomerieux: "The Virononstika HIV-1 assay reacts well with subtypes A-J of Group M strain. Also the assay can detect some of Group O strain. As for the MN or N strain, we do not have any information on this strain and we have no documentation that this assay can detect the N strain…The answer to your question regarding whether the antigens used in the Vironostika HIV-1 and Oral Fulid Vironostika assays are viral lysates or recombinant is that both assays contain antigens that are viral lysates." (5)

Note that: (i) the Voronostika "includes HIV-1 group O specific antigens" yet cannot detect even all the "Group O" "HIV-1" strains; (ii) since the antigens are "viral lysates" and since "HIV" has never been purified, the antigens could have originated from anywhere.

Christopher Noble wrote: "This test is widely used in Africa and was in fact was used in the Nelson Mandela/Human Sciences Research Council study of HIV/AIDS in South Africa. (8) As you are well aware as you have predictably criticised this study (9)."

It is true that we have criticised this study. A couple of the many important points to note are: (i) According to the manufacturers "The OraSure® HIV-1 pad is then placed in a vial with preservative and sent to a clinical laboratory for testing with an initial "screening" assay (ELISA)". The manufacturers of the Orasure System recommend "a supplementary test, the OraSure® HIV-1 Western blot assay, is performed to verify the result of the screening assay"; (ii) According to the manufacturers:

"Important Information OraSure® HIV-1 Oral Specimen Collection Device is intended for use in the collection of oral fluid specimens for testing for antibodies to the Human Immunodeficiency Virus-Type 1 (HIV-1) in subjects 13 years of age and older".

Regarding (i), the authors ignored doing any "supplementary…Western blot assay" and only on the basis of the "screening" test, they concluded that "the prevalence of HIV among persons aged two years and older is estimated at 11.4%" and the world has been repeatedly told that 5 million South Africans are infected with "HIV". (Note, in almost all countries of the world not even serum ELISAs are used to prove "HIV" infection. This is because "HIV" experts do not regard the test as specific).

Similarly, regarding (ii) the authors ignored the manufacturer’s "important information" regarding ages and on the basis of this test, they estimated the "HIV" prevalence among children aged 2-14 years to be 5.6%.

Even if one ignores all the other problems associated with the Nelson Mandela/HSRC study, the above points (i) and (ii) are sufficient for any scientist including Christopher Noble to be critical of this study. In fact, given the grave consequences of the conclusions reached in this study, it is the duty of scientists especially that of the "HIV" experts to rectify the situation.

Christopher Noble wrote: "It is indeed ironic that you quote an interview with Peter Duesberg in which he spends a large proportion of his time explaining exactly why your claims about viral isolation are preposterous (10)."So they are claiming way above what the standards are for the identification of a virus, or any microbe, as the cause of a disease. The standards are only that it's free of other possible microbial causes. By the time when Koch, with his own postulates, identified tuberculosis bacillus [as the cause of tuberculosis], believe me, it was not chemically clean. They didn't have the methods at all at the time for chemical purification. They didn't have sucrose gradients, as Eleni always talks about; they didn't have gels and they didn't have any of those things. They didn't even know what proteins were at that time. " "

Peter is talking about standards "for the identification of a virus, or any microbe, as the cause of a disease". We are talking about the standards required to prove the existence of a virus. The two are not the same.

Christopher Noble wrote: "With regards to your argument about genetic variation he states; " I'm afraid that if you followed that line of logic, then we wouldn't exist, either! What you are just describing, or she is describing to you, is nothing but what is called genetic polymorphism."It is truly an amazing skill to turn a rejection of your arguments into support by selectively quoting Peter Duesberg."

We present what Peter said about genomic variation and let the readers decide who is "selectively quoting" or responds "with out of context quotes":

"Duesberg: I'm afraid that if you followed that line of logic, then we wouldn't exist, either! What you are just describing, or she is describing to you, is nothing but what is called genetic polymorphism. No two human beings are alike, in that regard. We all differ from each other in numerous so-called point mutations, and minor mutations. It's called genetic polymorphism. It's true for humans, plants, viruses, bacteria, and everything alive. But there are many things you can't mutate and expect to remain a human, or even an HIV. It's a bit like a car. You can change the color of a car, or you can change the shape of the fenders or the taillights easily. But if you start leaving out the brakes, or leaving out the transmission or the engine, then you may have created an interesting mutant, but it won't function as a car. You will never see it on the freeway. It's somewhere in a garage. And the equivalent in biology is it won't be around. It doesn't exist anymore. So there is a range, a small range, in which you can mutate a-round without too much penalty. But as soon as you exceed it you are gone, and you are not an HIV any longer, or a human any longer. If you lose some significant human gene, then you are either dead or you are a monkey or what have you. You are not part of the species any longer. There's a lot of variability, but you're on a very tight leash in biology. If you get beyond that leash, then you have lost the essential characteristics that allow you to function as a life form.

It's true that viruses can vary much more than cells -- human, animal, plant or bacterial cells alike -- because cells are actually the responsible species that have to maintain a reasonable economy in everything to keep things going. A virus is only a parasite. All it needs to do is to take care of its own replication. So a virus has more flexibility to mutate than does a cell. It has to maintain a much smaller budget and a much smaller economy. But the rules in general are still the same. You can mutate certain things, and when you go beyond that, then it's over. It doesn't exist anymore. And, in that regard, HIV is exactly -- and I'm pointing out exactly -- the same as all other viruses. You'll find the same thing with flu and with polio and with measles and with mumps and with other retroviruses in chickens and in mice.

There is nothing special about HIV in that regard. Nothing." (6)

Christopher Noble wrote: "Please answer my simple and direct questions regarding regarding the genomes of poliovirus and influenza A. Please do not repond with out of context quotes."

Again, suppose for the sake of argument that there are published papers with evidence (and not merely evidence in databases) which prove that in RNA viruses the nucleic acid "sequences differ by approximately 50%" and that the viruses "differ from each other by 81% at the amino acid level". The problem then is how loose the "leash" can be before you start asking questions in regard to: (i) protein function. Not too loose according to Steinhauer and Holland (7) as well as Gallo and his associates.(8) (ii) defining "HIV" infection in molecular terms. Not too loose according to researchers from the Pasteur Institute.(9, 10) (iii) the viruses entry into "error catastrophe" or before they become monkeys, to paraphrase Peter Duesberg. Not too loose according to Peter and to Esteban Domingo.(11, 12)

So far Christopher has not addressed our basic questions regarding the evidence which is claimed to prove the existence of "HIV". Perhaps he may like to address the following: (i) let’s assume that there are viruses in which the nucleic acid "sequences differ by approximately 50%". Would it be possible then to define infection with these viruses in molecular terms? (ii) Let us assume that from cultures containing tissues that originated from AIDS patients, in sucrose gradients a 1.16gm/ml band has been obtained which contained nothing else but retrovirus-like particles. The particles have shown to be infectious and their genome to consist of RNA. Since the human genome contains endogenous retroviruses which can be expressed especially in cultures under the conditions used by "HIV" experts, Christopher Noble then like us will conclude that such viruses may not be exogenous and in fact may not be present in the AIDS patients. Would please Christopher Noble give us a blind control study and a few confirmatory studies with proof for the existence of the full length "HIV" genome in fresh, uncultured lymphocytes of AIDS patients?

References

1. Moore J P and Nara PL, (1991). The role of the V3 loop and gp120 in HIV infection. AIDS 5:S21-S33.

2. Mortimer PP, (1989). The AIDS virus and the AIDS test. Med. Internat. 56:2334-2339.

3. Rosenberg ZF and Fauci AS, (1990). Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. Immunol. Today 11:176-180.

4. Hausmann EHS, Gelderblom HR, Clapham PR, Pauli G and Weiss RA, (1987). Detection of HIV envelope specific proteins by immunoelectron microscopy and correlation with antibody titer and virus neutralizing activity. J. Virol. Meth. 16:125-137.

5. Correspondence between VF Turner and Biomerieux

6. http://www.virusmyth.net/aids/data/mcinterviewpd.htm

7. Steinhauer DA, Holland JJ. (1987). Rapid evolution of RNA viruses. Annual Review of Microbiology 41:409-33.

8. Ratner L, Haseltine W, Patarca R, Livak KJ, Starcich B, Josephs SF, Doran ER, Rafalski JA, Whitehorn EA, Baumeister K, Gallo RC, Wong-Staal F. (1985) Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature 313: 277-284.

9. Vartanian JP, Meyerhans A, Henry M, Wain-Hobson S. (1992) High-resolution structure of an HIV-1 quasispecies: identification of novel coding sequences. AIDS 6(10): 1095-1098.

10. Meyerhans A, Cheynier R, Albert J, Seth M, Kwok S, Sninsky J, et al. (1989) Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell 58(5): 901-910.

11. Domingo E. (2003) Quasispecies and the development of new antiviral strategies. Progress in Drug Research 60: 133-158.

12. Pariente N, Airaksinen A, Domingo E. (2003) Mutagenesis versus inhibition in the efficiency of extinction of foot-and-mouth disease virus. Journal of Virology 77(12): 7131-7138.

Competing interests: None declared