Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso
Send response to journal:
Basic requests which remain unanswered by Brian Foley and Christopher Noble
The many basic requests, which so far Brian Foley and Christopher Noble have failed to answer, include the following:
1. "Where are the experiments which prove HIV isolation, sexual transmission and antibody specificity?".
("A simple request from the Perth Group" - 5th June)
2. "Where are the experiments which prove HIV isolation and thus the existence of the HIV genome, sexual transmission and antibody specificity?
("The request remains the same and is still pure and simple" - 12th June)
3. "Where is the proof for HIV purification by any method?"
("Where is the proof for HIV purification by any method?" - 19th June)
4. "Could Brian Foley or anyone else please give us a few of the "thousands" of references where HIV-1 has been separated "from the vast majority of other material", in other words, purified?"
("A further plea for references on HIV purification" - 9th July)
5. "If so, we implore him [Brian Foley] to provide a few references that prove: (i) the molecules used in "cloning of a complete viral [HIV] genome" originated from HIV particles; (ii) cloning of HIV; (iii) the HIV "Genetic sequences" in his database originated from HIV particles….We would be grateful if Brian Foley could provide us with references showing HIV-1 preparations on which "No apparent differences in physics appearance could be discerned among the viral particles in these regions" as Sinoussi et al did and with "a high degree of homogeneity" and "virtual absence of DNA" as Crawford et al did….So we repeat "where is the proof for HIV purification by any method?" That is, give us the published references."
("References on HIV purification " - 3rd July)
6. "We are ignorant of the evidence which proves the existence of HIV. Would Christopher Noble please enlighten us with some references?"
("HIV" genomic variations - 31st July)
7. "We would be grateful if Brian Foley would provide us with references containing electron micrographs from either the 1.16gm/ml band or cultures showing identical HIV-1 M group and HIV-1 O group viruses….So we again ask if Brian Foley would provide us with references which prove that the “HIV” sequences originated from a unique infectious retroviral particle, HIV….All learning begins with being educated in the basics. The basic information we have been repeatedly asking for is the following:
(a) A few references which prove that the “purified HIV”, that is, the 1.16gm/ml band from which the “HIV” genome and proteins originated, contains particles in which “No apparent differences in physical appearance could be discerned” and the particles have the morphology of retroviruses.
(b) A few references that prove: (i) that the molecules used in “cloning of a complete viral [HIV] genome” originated from HIV particles; (ii) that the HIV “Genetic Sequences” in his databases originated from HIV particles.
(c) A few references which prove that the HIV antibody tests are specific. To claim proof for specificity there MUST BE at least one study and a few confirmatory studies where the antibody antigen reaction (assuming that the antigens are HIV) is compared with the present or absence of HIV, that is, with HIV isolation/purification. This study must include a statistically significant number of both patients who have AIDS as well as patients who do not have AIDS but are sick. In addition, the tests must be done blind.
(d) A few references which prove that HIV is heterosexually transmitted. Any study claiming proof for heterosexual transmission MUST satisfy at least the following conditions:
· Be prospective;
· Use tests which have been proven to be specific;
· Have a statistically meaningful population;
· The results must be statistically significant and must exclude any other possible route of infection;
· There should be at least a few confirmatory studies."
("Re: Politics vs. Science" - 5th August)
8. "As we have already pointed out to Brian Foley in our previous rapid response "HIV Genome, Clones and Sequences" (18 July 2003), what Montagnier’s and Gallo’s groups defined as "HIV" genome is nothing more than a poly(A)-RNA which in sucrose density gradients banded at the 1.16gm/ml. They claimed that the band represented "purified" virus but presented no EM proof. According to Montagnier the reason for this is because in the "purified" virus they could find no particles with the morphology typical of retroviruses….Would Brian Foley please answer the following question: Isn’t it true that this is how the "HIV" genome was obtained? If not, would Brian Foley please tell us where we are wrong?…. Since "HIV-1(MN)" has been used by laboratories around the world included Bess’ laboratory, in his view would Brian Foley please tell us which of Gallo’s evidence proves the existence of "HIV-1(MN)"? "
("Questions and Answers" - 13 October)
9. "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?"
("Genomic Variability" - 14th October)
10. "Would Christopher Noble tell us how then he can conclude that the gp41 found by Montagnier and Gallo to react with AIDS patients’ sera was an "HIV" protein?
To claim that gp41 is an "HIV" protein, then (i) proof must exist that it originated from a retrovirus particles or as Montagnier put it, from purified "HIV" particles; (ii) since cellular proteins can be incorporated in virus particles, proof must exist that the protein is coded by an RNA which originated from a retrovirus particle or "purified" virus particles.
Would Christopher Noble please give us a few references showing that points (i) and (ii) have been satisfied?"
("gp41" - 20th October)
11. "It is common knowledge that although initially Gallo implied that H9 was an original cell line developed in his laboratory, it is nothing more than a clone of HUT-78. Since Gallo and his associates were the first to introduce the “HIV” genes, we would be grateful if Christopher Noble reads their papers (8,9,10) and tell us what evidence presented in these papers proves beyond reasonable doubt the existence of the genome of a unique retrovirus and of its genes “gag,pol,vif,vpr,vpu, tat,rev,env,nef”. "
("More on Genomic Variability" - 23rd October)
12. "We have always thought that to prove the existence of the “HIV” virus, you have to isolate/purify it and then proceed to define its genome and genomic sequences and its proteins. Otherwise, how do you know that the genomic sequences are those of “HIV” and the proteins are coded by these sequences? It is obvious that you cannot start with impure material to define the origin of the genome. If Christopher Noble has another way would he please tell us what it is?"
("Did Montagnier prove the existence of "HIV"?" - 4th November)
13. "Viruses are not electrons. They are particles which can be seen using electron microscopes, can be obtained separate from everything else and their constituents determined precisely. The theory of electrons as negatively charged particles is a theory whose predictions have been tested and verified. Would Christopher Noble tell us what predictions of the “HIV” theory have been tested and verified?"
("Did Montagnier prove the existence of "HIV"?" - 4th November)
14. "Let us assume that Christopher Noble repeats Gallo’s and Montagnier’s experiments. That is, he takes the “viral lysate” and reacts it with AIDS patient sera. What will be the scientific basis for a conclusion that the protein of molecular weight of 41,000 which reacts with AIDS patient’s sera is not actin but a protein coded by the genome of a totally new virus?"
("More on "HIV" gp41" - 25th November)
15. "If the "density gradient ultracentrifugation and fractionation contain human proteins both from the cellular envelope…and from extra-viral material in the from of cellular vesicles and debris" how can anyone prove which of the proteins present there are "HIV" and which are cellular? How, from such a material which, as Bess has shown contains cellular poly(A)-RNA, could anyone obtain the "HIV" genes for protein production in bacteria?"
("Perth Group responses to Brian Foley" - 25th November)
16. "Once again, would Christopher Noble please give us the references "for viral isolation and sequencing" published in peer reviewed journals….(a) why is it that a test, the PCR, whose basis is claimed to be recognition of nucleotide sequences specific to an exogenous retrovirus HIV, "should NOT be used" even as a screening test in adults and adolescents and infants infected via blood transfusion yet is recommended and approved to prove perinatal transmission?
(b) why cannot the test be used even as a screening test to prove infection of children by means other than perinatal transmission but can be used to prove mother to child transmission? How it is possible for a PCR to discriminate between children infected perinatally and by other means?"
("Perth Group responses to Christopher Noble" - 25th November)
17. "Would then Brian Foley and Christopher Noble tell us whether in 1983 Montagnier discovered the biological entity now known as "HIV"? YES or NO. If yes, what is the evidence in his paper "that a virus, later called HIV, can be found in patients that have AIDS"? What is the evidence in his 1983 paper (1) that such a virus exists in anyone?"
("Has Montagnier discovered the Human Immunodeficiency Virus?" - 25th November)
The evidence we have been asking is at the very basis of HIV/AIDS. If such evidence does not exist there can be no "HIV" and thus no "HIV" theory of AIDS. Brian Foley and Christopher Noble posted many rapid responses, some of them of considerable length, but they have never answered our basic questions. Any scientist would ask then, why? What is going on?
It appears this debate is followed by some of the most eminent “HIV” experts. But, instead of participating they complain to Nature about the "sceptics" and criticise the British Medical Journal for doing what all medical and scientific journals should do: encourage scientific debate. Anybody would have to ask, why have they taken such an unusual step? What is going on?
Instead the experts advise “sceptics” are to be ignored and not given the opportunity to seek, via the scientific journals, the answers to the most basic questions (see correspondence sent to Nature below). Again, anybody would have to ask, what is going on?
Correspondence rejected by Nature
This correspondence was sent to Nature with comments in regard to a news item entitled “Medical journal under attack as dissenters seize AIDS platform” (November 20th 2003,page 215).
Eleni Papadopulos-Eleopulos, Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso.
In Declan Butler’s news item (20th November) he has included a scanning electron micrograph which, together with the legend, occupies some 22% of the article and this presumably reflects its importance. However, the source of the electron micrograph (EM) is not given, there are no labels and the magnification is not specified. The appearance of the cell in the micrograph is unlike any white blood cell that has ever traversed the vascular system and if the particles displayed are indeed HIV they are obviously on the cell and not in the cell as the author claims. Moreover, these surface particles are cylindrical and not spherical and are several microns in length and such appearances and dimensions would be not only unique to HIV but to any other retrovirus seen by electron microscopy. It is unlike Nature to feature reports in which the scientific rigor is minimal.
In 1984 one of the researchers predominantly featured in the news item, Wain-Hobson and his colleagues, claimed to have obtained “purified” HIV. In the “purified” virus they found a poly(A)-RNA and claimed that this RNA was the HIV genome.1 However, (i) although poly(A)-RNA is characteristic of retroviral genomes even Gallo agrees is it is not specific for retroviruses;2,3 (ii) no electron micrograph was published to show that the “purified” virus was free from impurities containing RNA; (iii) they had no controls; (iv) the only EM of “purified” HIV were published in 1997. These showed that the “purified” virus consisted predominantly of “budding membrane particles frequently called microvesicles” amongst which there are a small number of particles which the authors claimed are HIV but none of which have all the morphological characteristics attributed to HIV. Most importantly, microvesicles obtained from non-infected cells also contained poly(A)-RNA.4,5
According to John Moore, another prominent HIV researcher featured in the news item, “HIV-1 infection of CD4+ cells is initiated by interaction between its surface glycoprotein, gp120 and the cellular antigen CD4…On the virus surface, mature gp120/gp41 heterodimers are grouped together into oligomeric spikes that are clearly visible in electron micrographs”.6 However, to date nobody , not even Hans Gelderblom, could demonstrate that the surface of the “HIV-1” particles is studded with spikes much less with spikes containing “mature gp120/gp41 heterodimers”.7,8
The matter of the HIV particle infectivity and its genome is not trivial. Yet, according to the HIV experts, the “sceptics” “are best ignored”, a recommendation which extends to disregarding their publications in the peer reviewed scientific journals. Given the importance of this matter Nature could either seek clarification from the HIV experts or preferably arrange a scientific debate between the two sides adjudicated by disinterested scientists. In this manner the matter could be resolved once and for all.
1. Alizon, M. et al. Molecular cloning of lymphadenopathy-associated virus. Nature 312, 757-760 (1984).
2. Gillespie, D., Marshall, S. & Gallo, R. C. RNA of RNA tumor viruses contains poly A. Nature New Biol 236, 227-231 (1972).
3. Edmonds, M. A history of poly A sequences: from formation to factors to function. Prog Nucleic Acid Res Mol Biol 71, 285-389 (2002).
4. Bess, J. W., Gorelick, R. J., Bosche, W. J., Henderson, L. E. & Arthur, L. O. Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations. Virol 230, 134-144 (1997).
5. Gluschankof, P., Mondor, I., Gelderblom, H. R. & Sattentau, Q. J. Cell membrane vesicles are a major contaminant of gradient-enriched human immunodeficiency virus type-1 preparations. Virol 230, 125-133 (1997).
6. Moore, J. P. & Nara, P. L. The role of the V3 loop and gp120 in HIV infection. AIDS 5, S21-S33 (1991).
7. Layne, S. P. et al. Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus. Virol 189, 695-714 (1992).
8. Kuznetsov, Y. G., Victoria, J. G., Robinson, W. E., Jr. & McPherson, A. Atomic force microscopy investigation of human immunodeficiency virus (HIV) and HIV-infected lymphocytes. J Virol 77, 11896-909 (2003).
Competing interests: None declared