Re: Johnson on AIDS

Date: Wed Mar 19 2003 - 09:56:47 EST

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    Don Perrett wrote:

    > PJ aside, would you agree that there is a "conspiracy" (minor one perhaps)
    > to hold back on a cure?
    > Take Smallpox, eradicated, right?
    > How much money has the pharmaceutical companies and medical establishments
    > lost due to the lack of treatment for this disease? While I would not
    > agree with PJs conspiracy theory, I do believe that there are some in the
    > upper echelons of medicine that would prefer that AIDs not be cured. There
    > is more money in treatments than in cures. As a generality, on the
    > military researchers would gain from a cure, to protect troops. However
    > this does not mean they would give up the cure either. That would
    > relinquish their control over other military forces.

    I realize that it must be hard to understand how something can
    take so long to for so many scientists to figure out. I don't think
    most of the scientist who started on this some 25 years ago could
    imagine that it would take this much.

    A good part of the work force are academics and government labs.
    There would be a lot of incentive for such a scientist to find a
    solution because it gains recognition, funding and of course almost
    certainly a Nobel prize. Even for pharmaceutical companies, they
    have control over the patent.

    To conquer the HIV virus, we have to find some place in the retrovirus'
    life cycle to "throw a wrench into the machinery." Scientists have looked
    at a variety of points in the cycle, but the HIV retrovirus is particularly
    difficult to attack. The major reason is that in transcription of a retro-
    viral sequence, the reverse transcriptase seems to generate about one
    error per 10000 nt, and that is approximately the length of the HIV
    genome. So every copy that is made has potentially one mutation on

    About 1 billion sequences are generated per day. Contrary to what some
    people have been told, the mutations that are lethal are unusual and
    interesting for that reason. The majority of mutations are insignificant.
    Just consider that in the human genome there is what is called polymorphism,
    where there are small differences between the messenger RNA (mRNA) coding
    sequences of different individuals. Because of redundancies in the codons,
    some of these differences change nothing [although the concentrations
    of different transfer RNA (tRNA) molecules could make some very minor
    differences]. Now for the HIV retrovirus, those small differences in the
    mRNA coding sequence help allow it to make a highly variable protein coat
    for example. Lots of those subunits for building the protein coat are
    with most viruses and that is a good "foreign object" for the immunity system
    to quickly recognize as an impostor and forge an attack (for example).

    The immunity system usually finds an arm on a protein coat (for example)
    to grab onto (typically a turn or some other region on the surface
    of the protein), and for most viruses that spells "game over pal". Not for
    HIV keeps shuffling those regions so the immune system cannot keep up. It
    may even be that there are regions in the coding sequences of the mRNA that
    encourage higher mutation rates with the reverse transcriptase, but I really
    don't know, as we don't understand that mechanism all that well either. I
    wouldn't be surprised though, because the most promising antibodies do not
    the standard "Y" shape, but are more "I" shaped and penetrate much
    deeper into the protein structure.

    So with the above in mind, is it possible that pharmaceutical companies
    are trying to slow down the discovery of a cure? If the cure ultimately
    requires some individualized treatment, and there is no simple systematic
    way to manufacture these products, I might expect that pharmaceutical
    companies would see little incentive to pursue such a project. On the
    other hand, HIV as adaptive as it is, remains a general menace, and I
    would still see more profit in finding a weapon to fire on this monster,
    even if it is more like "bird shot". The only thing slowing this down
    is that a lot has already been invested with little or no return, so it
    falls more on government laboratories and die hard academics to patiently
    pursue the problem.

    by Grace alone we proceed,

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