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

[Brett Paatsch]

The Avantguardian wrote:

> --- 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. 

Couldn't that be legitimate? You do want existing treatments
to keep working, ie, you do want to overcome the drug
resistance while better solutions, if any, are not yet available
don't you?

>HIV is just 9.8
> kilobases of RNA that contains 8 genes that encode a
> little over a dozen protein products.

Okay, so how long has that been known. Not 19 years
I'd bet you. Not even 9 years, for all the genes, I'd still
be inclined to give you odds without checking ;-). 

> Of those, only
> reverse transcriptase and protease, both of which
> operate AFTER infection takes place, have been
> targeted by drugs.

Okay. 
 
> 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.

Say you are right. The AIDS patient is only hostage until
a better drug comes along, correct? In the meantime he or
she has a reprieve from dying which is different from facing
a threat to being killed by another person for ransom. 
  
> 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.

Do you understand how the pharmaceutical development
pipeline works from a commercialisation standpoint? 

Do you understand why it might take 5 years or more? 
Do you understand what hoops might have to be gone
through to get FDA approval for a treatment and perhaps
approval for even testing in human tissue?  I don't in detail
but I've got some idea and 5 years doesn't surprise me. Its
disappointing that things take that long but not surprising. 

> 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.

Aren't you in the US and curious about it? Don't you 
really mean know one else that you know?

 > 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.

Well thats gotta be good.  But how thorough is "pretty
thorough"? 

> 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.

You *think* you've identified a computer model of a 
protease inhibitor for an essential protein? 

What would it take to prove that you have? Does your 
HIV protein have an equivalent in an animal virus? If so
do you know that they aren't even now trying to 
demonstrate in an animal model what you only have 
on computer?

> Yet unbelievably, I have had several
> rejections from different university labs without the
> professor so much as wanting to see my model.

Perhaps I am not understanding. But there is a lot
of hype about how fast things are moving in terms
of genomes and proteomes etc that perhaps the people
you are talking to aren't impressed because they think
there are more promising things about to impress them.
 
> 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.

I don't think you can rely on scientists to hold some sort
of solidarity to keep milking the funding line. Scientists
are people with egos, and increasingly with aspirations
to make money as well. If there is a buck or some kudos
in finding a better way I think some scientists will try to
find it.  Perhaps they just may not be making a fuss about
it because they are trying to scoop their competitors in a 
commerical context. Or perhaps things have moved so
quickly in the generation of genomes and proteomes and
bioinformatics in the last few years that the research scientists
are themselves finding it difficult to pick up the new ways of
doing science and also commercialising any innovation. 

Scientists and venture capitalists typically come from different
knowledge domains. Even very smart people are likely to 
have found it hard to be confident that they were ahead of 
their competitors in the lab, and also able to commericalise.

Its hard to do everything well at the same time. 

> 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. 

But isn't it the case that it is extremely difficult even today
to work with the actual virus in human tissue. Because human
tissue isn't available to work with it in?
 
> 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.

Good. 

> 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.

As a retrovirus isn't there a lot of legitimate interest in 
using it as a viral vector? This doesn't seem unreasonable
to me.

I wonder if you are being *more* disillusioned than you
need to be.  Perhaps you might be underestimating some
of the difficulties in the adjoining knowledge domains that
are required to turn research into products because you
are still relatively young and haven't seen those problems
yet?

Brett Paatsch