Perth Group Responses to Christopher Noble 25 November 2003
Previous Rapid Response Next Rapid Response Top
Eleni Papadopulos-Eleopulos,
Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso

Send response to journal:
Re: Perth Group Responses to Christopher Noble

Perth Group responses to Christopher Noble


In his rapid response "More Repetition", 5th November, Christopher Noble wrote:  "Eleni Papadopulos-Eleopulos writes:  "Yet when we asked for published references supporting the 50% variations, in the only reference Christopher Noble provided and as the above quote shows, "the authors compared not only human influenza A viruses but also influenza A viruses of birds obtained at different times from around the world" and "the sequence differences were based upon several assumptions".  So where are the published references "of examples of human influenza A hemagglutinins that differ by approximately 50%"?  Is it sufficient to report genomic variability from databases or should not we also ask what are the biological consequences of these variabilities?  The question also arises are all these variables real or are at least some of them the result of errors in PCR and phylogenetic tree analysis?"


Christopher Noble responded “I have already explained several times that the two subtypes of hemagglutinin that are currently co-circulating in humans are as divergent from each other as any other pair of subtypes.  Your objections are just ad hoc excuses.  You want to ignore the evidence because it contradicts your claims.  The influenza sequence database ( ) contains 1348 sequences of Influenza A hemagglutinin isolated from human hosts.  I have previously picked an H1N1 and an H3N2 isolate at random and shown that the similarity between these two sequences is somewhere around 50%.  If you take any other pair of H1 and H3 sequences the results will be exactly the same - around 50% similarity.  Are you claiming that all of these sequences are just accidents?  A large proportion of these sequences have been published in peer reviewed journals.  The methods for viral isolation and sequencing are published in these papers.  The fact that they are also submitted to a sequence database that is available online is hardly a reason to question the validity of the evidence.  Indeed, the only reason you are questioning the evidence is that it contradicts your passionately defended beliefs.  You simply refuse to admit that you are wrong".


It is not possible to ignore evidence that we do not have.  Once again, would Christopher Noble please give us the references "for viral isolation and sequencing" published in peer reviewed journals.


Christopher Noble wrote:  "When Peter Duesberg stated "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."  He was entirely correct".


We agree.  But, for some unknown reason Christopher Noble forgot to mention that Peter also said:  "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…So there is a range, a small range, in which you can mutate around 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…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…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".


Christopher Noble wrote:  "You still refuse to answer simple questions regarding the genomes of influenza and polio viruses.  Now you expect me to answer rhetorical questions.  “Would Christopher Noble tell us whether in his view Montagnier proved the existence of a retrovirus "HIV" in 1983? (8)  If Christopher Noble avoids answering this question it will mean that in his view no such proof can be found in the 1983 paper by Montagnier and his associates"”.


He responded:  “I have never stated that this paper "proved" anything.  There is no such thing as absolute proof in science.  Certainly nobody can "prove" something to somebody that does not want to believe it.  Montagnier did however present evidence that a virus, later called HIV, can be found in patients that have AIDS.  Since 1983 the amount of evidence that has accumulated is overwhelming.  In exactly the same way there is no such thing as absolute proof for the existence of electrons.  I am curious to know why you are not demanding "proof" for the existence of electrons".


In our rapid response “Did Montagnier prove the existence of “HIV”?” 4 November 2003,  commenting on Christopher Noble’s analogy between “HIV” and electrons we wrote:  “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?”

No predictions can be made based on “HIV” as an infectious particle unless HIV experts agree what is the putative retrovirus particle.  In this regard it is important to note that Montagnier and his colleagues reported “HIV” initially as a typical type C particle,1 then as a type D particle2 and then as a Lentivirus.3  In 1984 Gallo and his colleagues reported “HIV” as a type C particle.4  However, in 1985 Gallo wrote:  "A possible unique feature of the virions is the cylindrical core observed in many presumably mature virions.  Virions having this type of core have been frequently reported for certain type D retroviruses, and in some instances, for type C retroviruses".5  Jay Levy reported “HIV” as a type D particle.6  Others at the University of California wrote that "AIDS virus isolated show morphologic characteristics of type C, type D and Lentiviruses".7 According to the other researchers "T-cells and macrophages handle the virus very differently.  In the T-cell, virus buds out of the external plasma membrane of the cell.  In the monocyte/macrophage cultures it buds into membrane-bound vesicles inside the cells".8  The latter is a description of a type A, retroviral particle.9  Thus the leading “HIV” experts have described “HIV” as a member of two subfamilies and three genera of Retroviridae.  These taxonomical differences imply that if “HIV” was a newly discovered mammal, it could have been either human, a gorilla or an orang-utan.  By consensus for more than a decade the HIV experts have been claiming that HIV is a Lentivirus.  However, according to one of the most recent studies the “HIV” particles “are virtually indistinguishable from virions of MuLV” (murine leukaemia virus), a type-C oncovirus.10 For more than 15 years we have been told that the “HIV” particles, like all retroviral particles, are spherical and their surfaces are studded with projections, spikes.  We have also been told that the spikes are composed of gp120 and are absolutely necessary for infectivity.   However, according to a paper published in the Journal of Virology in November this year, there are no spikes on the “HIV” particles.10


In his rapid response "Error Thresholds", 6 November, Christopher Noble wrote:

"Eleni Papadopulos-Eleopulos writes:  "Since Christopher Noble agrees with this view but says that we have misrepresented it would Christopher Noble tell us what number he regards as being the maximum allowable "error threshold" for RNA viruses?  Is it as much as 5% or 80% or a percentage in between?"


He responded:  “Eleni does not seem to understand the papers that she reads.  The "error threshold" does not relate to the genetic dissimilarity between highly divergent isolates of a virus such as HIV-1 group M and HIV-1 group O or influenza A H1N1 and influenza A H3N2 etc.  Rather, it relates to an upper limit to the error rate in replication.  HIV and other RNA viruses such as poliovirus have high mutation rates with somewhere around 0.1 and 1 mutations per genome per replication (0.01 - 0.001% of the genome per replication).  These are very different concepts and yet Eleni is conflating the two". 


We are fully aware that there are two different concepts.  However, we are also aware that one leads to the appearance of the other.


Christopher Noble wrote:  "The papers that Eleni has cited do not support her views.  The authors of these papers do not agree with her". 


Christopher Noble never told us why the authors of theses papers support his view and not ours.


Christopher Noble wrote:  "It looks impressive to quote snippets from papers and to put lots of references at the bottom of your post, however, it is important that you;  a) understand the papers, b) accurately describe the papers.  Eleni has done neither of these".


We would ask interested readers to read our rapid responses and make their own judgements in regard to our ability to understand the papers we study and to present the data accurately.


In his rapid response "PCR Specificity", 6th November, Christopher Noble wrote:  "Eleni Papadopulos-Eleopulos writes: "Would Christopher Noble also please explain the 0%-100% specificity of the PCR Test?"


He responds: “I have already explained how Eleni is attempting to mislead the readers of this forum.  She cites a meta-study of the use of PCR in the diagnosis of HIV infection. (1)  A variation of between 40-100% was seen in the specificity of PCR between various studies.  What Eleni does not tell you is that most of the studies showed close to 100% specificity (see figure 1).  A SMALL number of studies found a poorer specificity.  It is not surprising that some studies had poor results.  PCR is a complicated procedure and is prone to a number of technical problems.  The metastudy however showed that PCR can be highly specific.  Importantly the best studies in the meta-analysis (blinding, controls, etc) showed high specificity.  "In studies in which the design was rated as either 3 or 4, sensitivity ranged from 83% to 100% and specificity ranged from 95% to 100%".


In the meta-analysis study the authors "accepted positive results on conventional antibody tests (if they included a confirmatory Western Blot analysis or similar test) or viral cultures as high quality evidence of infection", that is, as a gold standard for PCR  In search of 17 computer databases, they "identified 5698 titles of potential relevant articles.  After independent review by two readers, 1735 titles were judged to be potentially relevant".  Then they "reviewed the associated abstracts and then selected 379 studies published as full articles for further review.  Of these 379 articles 96 met the inclusion criteria and were analysed".  Unlike Christopher Noble who claims that "The metastudy however showed that PCR can be highly specific", the authors of the study reported:  "When indeterminate PCR results were excluded, sensitivity ranged from 10% to 100% and specificity from 0% to 100%" and concluded "Our investigation produced two main findings.  First, the false-positive and false-negative rates of PCR that we determined are too high to warrant a broader role for PCR in either routine screening or in the confirmation of diagnosis of HIV infection.  This conclusion is true even for the results reported from more recent, high-quality studies that used commercially available, standardised PCR assays…We did not find evidence that the performance of PCR improved over time".11


Since there are no data proving the specificity of the antibody tests using HIV as a gold standard,  the antibody tests cannot be used as a gold standard for the PCR.12-15


In 1989, discussing their studies on human retroviruses, researchers from the University of New York wrote, "Irrespective of the origin of human retroviruses, their presence leads to both practical and theoretical concerns.  Presently, the major practical concern is that effective use of PCR as a screening procedure for HTLV-I, HTLV-II and HIV infections must always include appropriate controls to ensure that no endogenous sequences contribute to positive signals.  As previously noted, HIV unique primers corresponding to the highly conserved reverse transcriptase region…function well in the PCR amplification of HeLa DNA [a non-HIV-infected neoplastic cell line] even at annealing temperatures around 60°C.  Another practical concern is that the use of PCR for determining the possible retroviral etiology of a variety of human diseases may be complicated by endogenous retroviruses". 16


In an article where he discusses the laboratory diagnosis of "HIV infection", Philip Mortimer wrote:  "Other diagnostic methods, e.g. p24 antigen testing, and proviral DNA and RNA amplification exist, but these innovations in HIV diagnosis need to be matched against the anti-HIV [ANTIBODY] test and should be rejected unless they fulfil a need that antibody testing fails to meet".17


According to researchers from the University of London, "The use of polymerase chain reaction (PCR) for the diagnosis of HIV infection is becoming more widespread and although not yet entirely reliable compared with serology, has been of special value in HIV-seronegative intravenous drug users".18


If PCR needs to be matched against the "HIV" antibody test because it is less reliable that serology then, given the fact that a present there is no evidence which shows that a positive "HIV" antibody test is proof of HIV infection, one inevitable, although from a different perspective, must arrive at the same conclusion as Shoebridge et al.  "…until further molecular and biological studies are carried out, it will be unsure as to what detection of HIV-1 DNA, even when shown to be HIV-1 really means".19


According to one British researcher, "Those laboratories which undertaken HIV screening and confirmation assays understand fully the technical problems associated with PCR and other amplification assays and it is precisely for those reasons that PCR is NOT used as a confirmatory assay (as discussions with any competent virologist would have informed them)".20


In the 2000 Revised Surveillance Case Definition for HIV Infection it is stated:  "In adults, adolescents, and children infected by other than perinatal exposure, plasma viral RNA nucleic acid tests should NOT be used in lieu of licensed HIV screening tests (e.g. repeatedly reactive enzyme immunoassay)" (emphasis in original).21


The following questions arise:


(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?


Christopher Noble also wrote:  'The real question is how is this possible?  How does this amazing coincidental correlation between the detection of HIV RNA and anti-HIV antibodies occur?  Eleni would like people to believe that both of these measurements are non-specific yet they correlate so well.  Eleni would like people to believe that her theory predicts all the experimental phenomena associated with AIDS.  Does her theory predict this result?  I have previously asked Eleni to comment on this but she has remained silent".


To date we have left none of Christopher Noble's questions unanswered.  The only way to prove a correlation between the antibody test and the PCR is to perform blind controlled studies.  As far as we know, only one such study has been published to date.  In this investigation, Christine Defer from the Laboratorie d'Ingenierie Moleculaire, Centre Regional de Transfusion Sanguine including colleagues from the Pasteur Institute, studied PCR testing proficiency in "Seven French laboratories with extensive experience in PCR detection of HIV DNA".  Four groups of individuals were tested:  those with "unequivocal HIV-positive test results" (ELISA confirmed with Western Blot); "individuals at low risk of HIV infection who presented with a persistent and isolated anti-p24 antibody on Western blot"; "HIV-1 seronegative (on ELISA) individuals at low risk of HIV infection (blood donors)", and "seronegative (on ELISA) individuals at high risk of HIV infection (homosexual contacts of an HIV-seropositive partner".  From "two different peripheral blood mononuclear cell panels...each consisting of 20 samples", the authors compared PCR results in both seropositive and seronegative subjects.  The PCR was found to be non-reproducible, "False-positive and false-negative results were observed in all laboratories (concordance with serology ranged from 40 to 100%)", and "the number of positive PCR results did not differ significantly between high- and low-risk seronegatives". 22




1. Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220:868-71.

2. Klatzmann D, Barré-Sinoussi F, Nugeyre MT. Selective Tropism of Lymphadenopathy Associated Virus (LAV) for Helper-Inducer T Lymphocytes. Science 1984;225:59-63.

3. Montagnier L. Lymphadenopathy-Associated Virus: From Molecular Biology to Pathogenicity. Ann Int Med 1985;103(November):689-693.

4. Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, Isolation,and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS. Science 1984;224:497-500.

5. Gallo RC, Shaw GM, Markham PD. The Etiology of AIDS. In: DeVita VT, Hellman S, Rosenberg SA, editors. AIDS Etiology, Diagnosis, Treatment and Prevention. 1st ed. Philadelphia: J.B. Lippincott Company, 1985.

6. Levy J, Hoffman AD, Kramer SM, Landis JA, Shimabukuro JM, Oshiro L. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science 1984;225:840-842.

7. Munn RJ, Preston MA, Yamamoto JK, Gardner MB. Ultrastructural comparison of the retroviruses associated with human and simian acquired immunodeficiency syndromes. Lab Invest 1985;53:194-199.

8. Orenstein JM, Meltzer MS, Phipps T, Gendelman HE. Cytoplasmic assembly and accumulation of human immunodeficiency virus types 1 and 2 in recombinant human colony-stimulating factor-1-treated human monocytes: an ultrastructural study. J Virol 1988;62:2578-2586.

9. Frank H. Retroviridae. In: Nermut MV, Steven AC, editors. Animal Virus and Structure. Oxford: Elsevier, 1987:253-256.

10. Kuznetsov YG, Victoria JG, Robinson WE, Jr., McPherson A. Atomic force microscopy investigation of human immunodeficiency virus (HIV) and HIV-infected lymphocytes. J Virol 2003;77:11896-909.

11. Owens DK, Holodniy M, Garber AM, Scott J, Sonnad S, Moses L, et al. Polymerase chain reaction for the diagnosis of HIV infection in adults. A meta-analysis with recommendations for clinical practice and study design. Ann Int Med 1996;124(9):803-15.

12. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM. Is a positive Western blot proof of HIV infection? Biotechnology 1993;11:696-707.

13. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D. HIV antibodies: Further questions and a plea for clarification. Curr Med Res Opinion 1997;13:627-634.

14. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Causer D, Page B. HIV antibody tests and viral load - more unanswered questions and a further plea for clarification. Curr Med Res Opinion 1998;14:185-186.

15. Papadopulos-Eleopulos E, Turner VF, Papadimitriou JM, Alfonso H, Page BAP, Causer D, et al. High rates of HIV seropositivity in Africa-alternative explanation. Int J STD AIDS 2003;14:426-427.

16. Shih A, Misra R, Rush MG. Detection of multiple, novel reverse transcriptase coding sequences in human nucleic acids: relation to primate retroviruses. J Virol 1989;63:64-75.

17. Mortimer PP. Ten years of laboratory diagnosis of HIV: how accurate is it now? J Antimicrob Chemother 1996;37:B. 27-32.

18. Boriskin YS, Booth JC, Roberts MM, Carrington D, Coates ARM. HIV primers can amplify sequences of human satellite DNA. AIDS 1994;8:709-711.

19. Shoebridge GI, Barone L, Wing-Simpson A, Bennetts BH, Nighingale BN, Hensley WJ, et al. Assessment of HIV status using the polymerase chain reaction in antibody-positive patients and high-risk antibody-negative haemophiliacs. AIDS 1991;5:221-224.

20. Chrystie IL. Screening of pregnant women: the case against. Pract Midwife 1999;2:38-39.

21. CDC. Guidelines for national human immunodeficiency virus case surveillance, including monitoring for human immunodeficiency virus infection and acquired immunodeficiency syndrome. Centers for Disease Control and Prevention. Morb Mortal Wkly Rep 1999;48(RR-13):1-27, 29-31.

22. Defer C, Agut H, Garbarg-Chenon A, Moncany M, Morinet F, Vignon D, et al. Multicentre quality control of polymerase chain reaction for detection of HIV DNA. AIDS 1992;6:659-663.


Competing interests: None declared