[extropy-chat] The Hidden Luddite was Re: peak oil debate

[The Avantguardian]

--- BillK <pharos at gmail.com> wrote:

> 
> More than 20 million people have died of AIDS since
> 1981.
> AIDS deaths in 2004, estimated at 3.1 million.
> 
> You *really* think some people are deciding not to
> bother finding a
> cure because they can make a bit of money on the
> deal?

Well, Bill, I wish I could think differently. I will
tell you one thing for certain. Reverse transcriptase
inhibitors like AZT were invented about 19 years ago,
protease inhibitors like Sequinovir were invented 10
years ago. Since then about the most anyone has done
is when David Ho figured out you can slow down the
evolution of drug resitant virus within a patient by
giving them both at once. Hardly a leap of genius but
he got Time's "man of year " award and lots of grant
funding out of it. 

Every couple of years, the pharmaceuticals tweak their
RT and protease inhibitors a bit to overcome drug
resistance and that's about it. HIV is just 9.8
kilobases of RNA that contains 8 genes that encode a
little over a dozen protein products. Of those, only
reverse transcriptase and protease, both of which
operate AFTER infection takes place, have been
targeted by drugs.

The end result of these drugs is that the virus goes
into latency, and hides in the patient's cells. It
remains hidden away until the person stops taking the
drug and voila out pops the virus, left unchecked will
go on to kill the person. The AIDS patient is now
hostage to his drugs.
  
There are plenty of other HIV proteins that COULD be
targeted with drugs. There are several inhibitors of
the virus integrase protein in the pipeline, but
apparently they have some bad side effects because
they have been in the pipeline for about 5 yrs now and
I don't know when or if they will ever become
available. Integrase however is another example of a
virus protein that operates AFTER the virus infects a
cell. 

HIV makes a little over a dozen protein products
(which is amazing considering that it is a single
9.8kb RNA, making it the most informationally dense
organism that has been sequenced to date) including
some that operate BEFORE or DURING infection. Yet
nobody in the U.S. is trying to target any of these
despite the fact that they would kill the virus BEFORE
the virus can hijack the host cell. If these other
proteins had been tried and failed due to technical
problems that would be one thing, but nobody in the
U.S. is apparently even curious about inhibiting any
of these.

I would not believe it myself except that for the last
7 yrs (essentially my entire career) I have been
studying both HIV virology and immunology and I have a
pretty thorough understanding of the virus. I think I
have identified its Achilles` heel and have computer
models of a potential inhibitor for an essential viral
protein that not only allows the virus to get into
cells, but also sows chaos and confusion amongst the
antibodies and whiteblood cells that are supposed to
kill the virus. Yet unbelievably, I have had several
rejections from different university labs without the
professor so much as wanting to see my model.

That is when it hit me. You can't give hundreds of
millions of dollars to a bunch of "experts" to poke
and prod the virus and expect them to cure it because
they know that if they do, the grant money stops.
We've poked and prodded the virus for over 20 years
now. We know every bit of its genome, we know what all
its proteins are and what cellular proteins they
interact with, we know its life cycle, we know how it
evades the immune system, and we can even take the
virus apart and reverse engineer the thing into a
gene-therapy vector. 

We have over 1500 publications regarding mechanism for
every gene the virus has, which is an order of
magnitude more than we have for the genome of any
other organism on earth. Yet amazingly we can't KILL
this one piece of RNA? You do the math. I went into
AIDS research hoping to cure the virus. Instead what I
found is that wracking ones mind to figure out new and
innovative ways to poke and prod at the virus are
rewarded and sincere ideas aimed at just plain killing
it are shunned. Its a lesson, I hope my career can
recover from.
     


The Avantguardian 
is 
Stuart LaForge
alt email: stuart"AT"ucla.edu

"The surest sign of intelligent life in the universe is that they haven't attempted to contact us." 
-Bill Watterson

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