BACK
DUESBERG CLAIMS CONTINUUM
AWARD
In 1983, Montagnier et al isolated a retrovirus, now termed Human
immunodeficiency virus (HIV), from a patient with lymphadenopathy and
proposed that HIV may cause AIDS. Antibody against this virus has since
been found in many, but not all AIDS patients (1) and in 17 million
healthy people (2).
Eleni Papadopulos, Val Turner, John Papadimitriou, David Causer,
Bruce Hedland-Thomas & Barry Page (3) and Stefan Lanka (4) maintain
that the very existence of HIV is dubious because (i) HIV has not been
properly isolated and thus could not have been properly identified
(according to Papadopulos et al: "HIV has never been isolated as an
independent particle separate from everything else"(3)); and (ii)
antibodies against HIV are not specific (5). They submit that the
following evidence is not "specific" for HIV: identifying in the growth
medium of infected human cell cultures either the existence of
virus-like particles with the electron microscope, or of reverse
transcriptase associated with such particles, or of certain HIV antigens
or proteins associated with particles, because each of these could be
cellular materials or could be from cell-borne (endogenous) retroviruses
other than HIV.
Indeed, each of these criteria could reflect another retrovirus, and
some of these criteria, eg. particles and proteins, could reflect
non-viral material altogether.
However, the Papadopulos-Lanka challenge, that HIV does not exist,
fails to explain (i) why virtually all people who contain HIV DNA also
contain antibodies against Montagnier's HIV strain - the global standard
of all HIV tests - and (ii) why most, but certainly not all people who
lack HIV DNA contain no such antibodies. The presence of HIV-reactive
antibodies in some uninfected people reflects an inherent limitation of
tests for antibodies against viruses and other microbes. Since even the
simplest microbes display thousands of antibody docking sites, termed
"epitopes", antibodies against a given microbe may cross react with an
otherwise unrelated microbe if the two share some epitopes.
In view of the current controversy about the identification of HIV,
the British AIDS magazine Continuum has offered in its Jan/Feb 1996
issue a "Missing virus! £1000 reward"(6) for proof of the isolation of
HIV, and the reward was reposted "105 days later...we're still
waiting"(7) in the March/April, 1996 issue together with my preliminary
"reward claim... Cordially yours, Peter Duesberg"(8,9). The stakes have
since been raised considerably by a private reward of £10,000 from Alex
Russell from the DMS Watson Library, University College, London (10),
and have now been raised even further by a £25,000 reward from James
Whitehead from the International AIDS Freedom Network (IAFN), London
(11,12).
Here I take up these challenges. I will argue that HIV exists, and
has been properly identified as a unique retrovirus on the grounds that
(i) it has been isolated - even from its own virion structure - in the
form of an infectious, molecularly cloned HIV DNA that is able to induce
the synthesis of a reverse transcriptase containing virion, and (ii)
that HIV-specific, viral DNA can be identified only in infected, but not
in uninfected human cells. In view of this I can base my claim for the
isolation of HIV on the most rigorous method available to date, i.e.
molecular cloning of infectious HIV DNA, rather than only on the much
less stringent, traditional "rules for isolation of a retrovirus ...
discussed at the Pasteur Institute, Paris, in 1973" that were stated
criteria of isolation in Continuum's missing virus reward (6). Indeed I
will show that molecular cloning of infectious HIV DNA exceeds the
criteria of the old "Pasteur rules".
(I) Isolation of HIV
The existence of the retrovirus HIV predicts that HIV DNA can be
isolated from the chromosomal DNA of infected cells. This prediction has
been confirmed as follows: Full-length HIV-1 and HIV-2 DNAs have been
prepared from virus-infected cells and cloned in bacterial plasmids
(13-15). Such clones are totally free of all viral and cellular
proteins, and cellular contaminants that co-purify with virus. These
clones produce infectious virus that is neutralized by specific antisera
from AIDS patients. For example, virus produced by infectious HIV-2 DNA
is neutralized by antiserum from HIV-2 but not from HIV-1-infected
people (15).
Since infectious HIV DNA has been isolated from infected human cells
that is free of HIV's own proteins and RNA as well as from all cellular
macromolecules, HIV isolation has passed the most vigorous standards
available today. In other words these infectious DNA clones meet and
exceed the isolation standards of the traditional "Pasteur rules".
Isolation of infectious HIV DNAs is theoretically the most absolute form
of isolation - it is the equivalent of isolating the virus' soul, its
genetic code, from the virus' body, the virus particle. Thus HIV
isolation based on molecular cloning exceeds the old standards defined
as "Pasteur rules" by Continuum.
(II) Identification of HIV
The existence of HIV predicts that infected cells contain a unique,
virus-specific DNA of 9150 nucleotides that cannot be detected in DNA of
uninfected human cells. The probabilities that cellular DNA and other
viral DNAs would contain the same sequence of 9150 nucleotides is 1 in
4E9150, or 1 in 10E4500 - extremely close to zero! Since the odds that a
given nucleotide of any DNA is either A, G, C or T are in 1 in 4, the
odds that any DNA has the same sequence of 9150 nucleotides as HIV-1 or
HIV-2 are only 1 in 4E9150.
Thanks to the outrageous interest in HIV as the hypothetical cause of
AIDS, many investigators have sought specific HIV DNA in humans with and
without AIDS in an effort to confirm that rather unreliable HIV
antibody-test (1, 5).
But because only 1 in 100 T-cells are ever infected in humans,
virtually all such studies use Kary Mullis' polymerase chain reaction, a
technique that is designed to amplify a DNA-needle into a DNA-haystack.
Such efforts have confirmed the existence of HIV-specific DNA in most
(not all) antibody-positive persons with and without AIDS - but not in
the DNA of antibody-negative people. For example Jackson et al have
tested blood of 409 antibody-posuitives including 144 AIDS patients and
265 healthy people. In addition 131 antibody-negatives were tested.
HIV-specific DNA subsets - defined in size and sequence by HIV-specific
primers (start signals for the selective amplification) - were found in
403 of the 409 antibody-positives, but in none of the 131
antibody-negative people (16).
The high sequence specificity of HIV DNAs is translated into the
specificity of their proteins, eg. antibodies against HIV-1 do not
neutralize HIV-1 (sic) and vice versa (15).
In Conclusion
HIV has been isolated by the most rigorous method science has to
offer. An infectious DNA of 9.15 kilo bases (kb) has been cloned from
the cells of HIV-antibody-positive persons, that - upon transfection -
induces the synthesis of an unique retrovirus. This DNA "isolates" HIV
from all cellular molecules, even from viral proteins and RNA. Having
cloned infectious DNA of HIV is as much isolation of HIV as one could
possibly get. The retrovirus encoded by this infectious DNA reacts with
the same antibodies that cross-react with Montagnier's global HIV
standard, produced by immortal cell lines in many labs and companies
around the world for the HIV-test. This confirms the existence of the
retrovirus HIV.
The uniqueness of HIV is confirmed by the detection of HIV-specific
DNA sequences in the DNA of most antibody positive people. The same DNA
is not found in uninfected humans, and the probability to find such a
sequence in any DNA sample is 1 in 4E9500 - which is much less likely
than to encounter the same water molecule twice by swimming in the
Pacific ocean every day of your life.
The existence of an unique retrovirus HIV provides a plausible
explanation for the good (not perfect) correlation between the existence
of HIV DNA and antibodies against it in thousands of people that have
been subjected to both tests. The Papadopulos-Lanka challenge fails to
explain this correlation.
Ergo: The Papadopulos-Lanka challenge is rejected. HIV exists and has
been isolated. *
Peter Duesberg
Source: Continuum July./Aug. 1996
References
1. Duesberg PH: The HIV gap in national statistics.
Bio/Technology 11:955-956 (1993).
2. World Health Organisation: The current Global
Situation of the HIV/AIDS Pandemic. Geneva (Jan 1995).
3. Papadopulos-Eleopulos E, Turner VF, Papadimitriou
JM, Causer D, Hedland-Thomas B and Page BAP: A critical analysis of the
HIV-T4-cell-AIDS hypothesis, Genetica 95:5-24 (1995).
4. Lanka S: HIV reality or artifact? Continuum 3/1:4-9
(April/May 1995).
5. Papadopulos-Eleopulos E, Turner VF and Papadimitriou
JM: Is a positive Western blot proof of HIV infection? Bioi?technology
11:696-707 (1993).
6. The Jody Wells Memorial Prize: Missing Virus! £1,000
Reward. Continuum 3/5:4 (Jan/Feb 1996).
7. Christie H: 105 days... we're still waiting.
Continuum 3/6:5 (March/April 1996).
8. Duesberg P: Reward Claim (letter). Continuum 3/6:18
(Mar/April 1996).
9. Christie H: Letter to Peter Duesberg (1996).
10. Alex Russell: Letter to Peter Duesberg (2/28/96).
11. Letter from Fred Cline, San Francisco,
Representative of the IAFN (2/4/96).
12. Alex Russell: Letter to Fred Cline, undated (April
1996).
13. Fisher AG, Collalti E, Ratner L, Gallo RC and
Wong-Staal F: A molecular clone of HTLV-III with biological activity.
Nature (London) 316:262-265 (1985).
14. Levy JA, Cheng-Mayer C, Dina D and Luciw PA: AIDS
retrovirus (ARV-2) clone replicates in transfected human and animal
fibroblasts. Science 232:998-1001 (1986).
15. Barnett SW, Quiroga M, Werner Am, Dina D and Levy
JA: Distinguishing features of an infectious molecular clone of the
highly divergent and non0-cytopathic human immunodeficiency virus type 2
UC1 strain. J Virol. 67:1006-1014 (1993).
16. Jackson JB, Kwok SY, Sninsky JJ, Hopsicker JS,
Sannerud KJ, Rhame FS, Henry J, Simpson M and Balfour HH Jr.: Human
immunodeficiency virus type 1 detected in all seropositive symptomatic
and asymptomatic individuals. J. Clin. Microbiol. 28:16-19
(1990).