Department of Medical Physics, Royal Perth Hospital, Western Australia 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso
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In his rapid responses “The Perth Group “answer” to Christopher Noble” (5, September 2003 and 12 September 2003), Christopher Noble wrote:
“You have claimed: "By comparison, two RNA containing viruses (polio and influenza, the latter after 27 years of dormancy,) vary by less than 1%" “
We have performed a search of all the rapid responses and could not find this quote attributed to us (apart from the two rapid responses of Christopher Noble).
In his rapid response “HIV genomic variations” (5 September 2003), Christopher Noble wrote:
“I obtained my copy of this article (1) from an Australian library. Please get the article and read it…Let me be absolutely clear. You consistently misrepresent the papers that I have provided if you even bother to read them.”
We have read all the papers including “article (1)” which is obvious from the fact that we have quoted extensively from them including “article (1)” in our rapid responses.
Most of Christopher Noble’s arguments are based on nucleotide databases and phylogenetic trees.
Since: (a) it is not sufficient to just look at databases and phylogenetic trees of influenza A, papilloma, polio viruses, but one has to determine the origin of the sequences and the method used in phylogenetic analysis; (b) we are not interested in these viruses and the topic of this debate is “HIV”;
we will leave it to others to pursue further investigations of the nucleotide sequences in the databases and the phylogenetic trees of these viruses. In searching and investigating databases and phylogenetic trees we should be cognisant of what Sir John Maddox, the former editor of Nature wrote: "Is there a danger, in molecular biology, that the accumulation of data will get so far ahead of its assimilation into a conceptual framework that the data will eventually prove an encumbrance? Part of the trouble is that excitement of the chase leaves little time for reflection. And there are grants for producing data, but hardly any for standing back in contemplation". (1)
Christopher Noble also wrote: “If you had bothered to actually read the paper on Influenza A that I cited (3) you would have seen in figure 6 that the subtype H3 (A/Texas/1/77) hemagglutinin is as distant from subtypes H1 (A/New Jersey/11/76) as any of the others. I take it you understand what a phylogenetic tree is? Both of these strains are isolated from humans at approximately the same time. If you had bothered to look at table 3 you would have seen that these two subtypes of hemagglutinin from influenza A, isolated from humans at approximately the same time, differ from each other by 81% at the amino acid level.”
According to the researchers from the Los Alamos National Laboratory: “Within a single 9 month flu season, little variation was typically found between geographically distinct influenza isolates after the emergence of the epidemic strain.” (2)
In the review paper “Rapid Evolution of RNA Viruses” where about 1% variation is considered to be “extreme heterogeneity”, the authors wrote: “the relative growth rate of a variant must be extremely close to that of the wild type (within 0.01-0.1%) in order to be detected by ordinary sequencing of the equilibrium population…Many selective forces may stabilize virus populations. These stabilizing factors may include the need for conservation of protein structure and function, RNA secondary structure, glycosylation sites and phosphorylation sites.” (3)
In 1985, Gallo and his colleagues wrote: “A comparison of clones BH8 and BH5 with BH10 demonstrates a 0.9% base pair polymorphism in the coding regions of the genome…The resultant differences in viral protein function remain to be determined.” (4)
In the view of one of the most eminent retrovirologists, Peter Duesberg: "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 HIV any longer, or a human any longer...then you are either dead or you are a monkey, or what have you". (5)
According to Esteban Domingo, one of the first researchers to search for variability in the genome of RNA viruses and to apply Eigen’s quasispecies concept to the genome of RNA viruses: “RNA viruses replicate near the error threshold for maintenance of genetic information, and an increase in mutation frequency during replication may drive RNA viruses to extinction in a process termed lethal mutagenesis.” Or “virus entry into error catastrophe”. Because of this he advocates the use of mutogenetic agents as anti-viral. (6,7)
This led us to consider the “extraordinary scale of HIV variation” (2) and to ask the questions: “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?” Christopher Noble has not answered these questions.
In his rapid response “The Perth Group “answer” to Christopher Noble” (12 September 2003), Christopher Noble wrote: “These sequences are available for anyone to check. The evidence is right there but you refuse to see it. If you refuse to accept this then there is no point in delving into etymological discussions about the meaning of the word 'isolation'.”
Nucleic acid sequences and phylogenetic trees are meaningless unless there is proof that they originated from virus particles. This proof can only be obtained by isolating/purifying them. Unless Christopher Noble comes up with a few references which prove “HIV” isolation/purification there is no point in debating nucleic acid sequences and phylogenetic trees.
(1) Maddox J. (1988) Finding wood among the trees. Nature 335:11.
(2) Korber B, Gaschen B, Yusim K, Thakallapally R, Kesmir C, Detours V. (2001). Evolutionary and immunological implications of contemporary HIV-1 variation. British Medical Bulletin 58: 19-42.
(3) Steinhauer DA, Holland JJ. (1987). Rapid evolution of RNA viruses. Annual Review of Microbiology 41:409-33.
(4) 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.
(5) Conlan M. Interview with Peter Duesberg. Reappraising AIDS 1998 (February/March). www.virusmyth.net/aids/data/mcinterviewpd.htm
(6) 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: 7131-7138.
(7) Domingo E. (2003) Quasispecies and the development of new antiviral strategies. Progress in Drug Research 60: 133-158.
Competing interests: None declared