Re: Out of all the Responses Four Arguments Have Emerged. Three of These Things are not Like the Other... 24 March 2004
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Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos, NM 87545

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Re: Re: Out of all the Responses Four Arguments Have Emerged. Three of These Things are not Like the Other...

Tony Floyd has accurately summed up the areguments, presented not only here but on at least one hundred web sites areound the world, and in numerous books.

It is my opinion that he is not correct in stating that only conspiracy theorists can be convinced that HIV has not been sufficiently implicated as the cause of AIDS. The various web sites and books written claiming that the cause of AIDS is not HIV, or not yet "proven" to be the cause, are not written by unintelligent people. The authors may either be knowingly telling lies, or they may just be ignorant of how biology/virology/epidemiology is done, but they are very clever in making their arguments such that many other intelligent people who also do not underestand biology are convinced.

This phenomena is not unique to the HIV/AIDS "debate". It is also seen in evolution vs. various forms of creationism including "intelligent design". It is seen in the multi-million dollar per year industry of selling books which claim various non-medical "cures" for cancer. Some of the "make money fast" scams are similar. What they all have in common is using an underlying motivation in making their cases. We would all love to believe that there is no AIDS and that the whole pandemic will just go away if we deny that HIV exists or is the cause, just as we would all love to believe that we can get rich without working, or that we can cure cancer by praying. People who have cnacer or are told they are infected with a virus that causes a terrible syndrome in a majority of untreated patients have a HUGE motivation to believe that this is not true. Denial may not be 100% "rational" or "scientific", but it seems to be hard-wired into the human psyche.

My guess is that over 90% of the 6+ billion people who currently live on earth do not have sufficient education in biology to know the difference between an antigen and an antibody, let alone to know how monoclonal antibodies played an important role in the "biological revolution" of the late 20th century. Many people in the industrialized world work with computers at home or at work on a daily basis, and thus have at least a little first-hand experience with the leaps that computer and communications technology has made in the past 20 years. Very few understand what cloning, sequencing genes, using monoclonal antibodies, phage display, yeast two-hybrid systems, DNA sequence databases, and other tools of the molecular biology and bioinformatics trades have done for biology and medicine.

Much of the HIV/AIDS "debate" is centered around the idea that a few months work by Robert Gallo and Luc Montagnier in 1983-1984 was the be-all and end-all of the "proof" that HIV-1 is the cause of AIDS. In reality, there was a tremendous ammount of information gathered between 1981 and 1983 that had already proven that AIDS was caused by a blood-borne pathogen that could pass through a filter (i.e. most likely a virus, but still possibly a mycoplasma or some life form unlike any other yet discovered). The "breakthough" in 1983 that lead to our ability to begin to isolate, characterize, and study lentiviruses including HIV-1, was the discovery that they grew almost only in stimulated T-cells. They cannot be cultured on the standard cell lines (most typically fibroblasts, but also kidney cells and a vast array of continuous cancer cell lines), and only a few strains are able to replicate in "resting" T-cells.

Gallo and Montagnier are credited with "discovering" HIV-1 because they were the heads of relatively large labs in which many people worked together to learn how to culture and thus "isolate" (in the sense that the virus was isolated in a petri dish, not in the sense that the virus was made 100% "pure") the virus, such that researchers could begin to study it. A viral culture does not have to be "pure" in the Perth Group sense of the word. We only need to know that we can pass the cell-free filtered supernatant from a virus-infected culture to a (or many) virus-free cultures in series. Next come steps showing that the infected, but not the uninfected cultures produce proteins that are reactive with the antibodies of AIDS patients (or pre-AIDS infected people such as people who had received transfusions from people who had AIDS or developed AIDS soon after donating their blood), but not reactive to antibodies to poeple who had not been exposed. This does not require that the virus pe 100% "pure", only that there are some proteins in the infected cultures that are not in the non-infected cultures.

The next step is making an infectious molecular clone of the virus, which may or may not be preceded by cloning and sequencing viral fragments, which can be useful in detecting which plasmids in a library are likely to contain infectious molecular clones.

Electron micrographs of sucrose gradient ultracentrifuge fractions are useful in determining if the isolated organism looks like a virus. But that is about all it is good for. Virus preparations that look as if they are 100% "pure" can still be mixtures of two or more different viruses, such as an oncoretrovirus and its helper. 100% pure virus preparations could be produced by an activated endogenous retrovirus. 100% pure virus preparations also contain host cell proteins in addition to proteins encoded by the viral genome. For example all enveloped viruses including retroviruses will carry host cell envelope proteins such as MHC molecules. Another example is that HIV-1 M group viruses package a few host cell proteins such as cyclophilin A, which are required for viral replication. See for example:

Zander K, Sherman MP, Tessmer U, Bruns K, Wray V, Prechtel AT, Schubert E, Henklein P, Luban J, Neidleman J, Greene WC, Schubert U.
Cyclophilin A interacts with HIV-1 Vpr and is required for its functional expression.
J Biol Chem. 2003 Oct 31;278(44):43202-13.

Khan M, Garcia-Barrio M, Powell MD.
Treatment of human immunodeficiency virus type 1 virions depleted of cyclophilin A by natural endogenous reverse transcription restores infectivity.
J Virol. 2003 Apr;77(7):4431-4.

The point is that it is highly ironic that the Perth Groups arguments in favor of using EM as the primary determinant of virus "purity", are actually arguments that explain why infectious molecular clones, pure HIV genome free of proteins, are very important if not critical in dtermining which virion proteins are derived from the viral genome, and which are derived from the host. The viral DNA sequences are also absolutely critical for determining whether the virus is derived from an endogenous retroviral genome, and if not which class of exogenous viruses it belongs to. Serology is the next best thing, and what the virus looks like under EM is nearly useless.

Competing interests: None declared