Wednesday, August 17, 2005


This guy Wilhelm is a supposed virologist, but in the discussions I've seen he's at best half-educated in the field.

Firstly he makes the old mistake of assuming that the nucleoside analogues (RTIs like AZT) are DNA chain terminators primarily. They are not, they are reverse-transcriptase inhibitors primarily, and they act by chain termination. Am I nit-picking? No - and here's why.

You probably have a car right? You probably use a key to get into and start your car, right? Does your key work on your neighbour's car? No? Why - because it fits only your car.

The same is true of drugs like AZT, they cannot possible act on a DNA chain unless they are placed in position and chemically altered to join the DNA chain. The positioning and altering is done by enzymes like HIV reverse transcriptase (RT) and cellular DNA polymerase. AZT doesn't fit DNA polymerase. AZT does fit RT. This can be shown in chemical assays and in tissue cultures - AZT and other similar drugs are many more times effective against the virus than against the cells (some cross-reactivity with cellular enzymes is almost inevitable, but even here AZT isn't even the worst...!)

So not only will AZT not work to chain-terminate unless HIV RT is present, it will ONLY work on the DNA chain that is linked to the viral enzyme! So antiviral drugs like AZT are very specific to the virus, and act directly against it.

Wilhelm speaks as if AZT acts on the proviral DNA. It can't possibly do that, because by the time the provirus is there, reverse-transcription has already finished. The only way you can reduce proviral load is to kill off infected cells. The Perth Group in fact try to argue this same point in their anti-AZT critique and state the obvious - if you close the stable door when the horse is in the pasture you can't reduce the number of horses in the pasture... Stupid bastards.

He's also obviously ignorant that the protease inhibitors were the first "designer drugs", drugs that were designed on a computer to chemically match the target enzyme (the viral protease) rather than any other similar enzyme. These drugs are the best example of virus-specific drugs out there! Viruses do indeed use the cell's machinery to replicate, but many viruses also carry their own essential enzymes that aren't found in the cells. HIV carries three of them, of which two are currently attacked by drugs (reverse transcriptase, protease, integrase). It also has several accessory proteins that aren't enzymes but are essential for HIV to replicate. These too can be targetted, at least in the lab. The most important two are called Tat and Rev. They may become future drug targets as well.

His comparison between bacteria and viruses is absurd. Bacteria do mutate, but their mutations are also completely random. What they do which many viruses do not is acquire large chunks of new DNA in the form of plasmids. These can spread antibiotic resistance very easily, even between different species of bacteria. Bacteria can no more "adapt" to a new environment than we can. Do we grow gills when we're drowning? No. But if you hand us a snorkel or scuba gear we can do quite well! Antibiotic resistance plasmids are the bacterial scuba gear.

All mutations are random, in bacteria, viruses and human beings. Viruses in fact are far superior to bacteria in the rate of mutation at the nucleotide level because they replicate at far higher rates. When you have several thousand progeny, it doesn't take many rounds of replication to come up with an advantageous mutation such as a drug-resistant enzyme. The defective viruses will die, and in the face of drug therapy so will the neutral viruses, leaving only the resistant ones. It's called Darwinian selection - survival of the fittest.

If a resistant bacterial colony appears on an agar plate it is not because the bacteria "developed" resistance, its because among the bacteria that were present all the non-resistant ones died off, leaving the resistant one to take over.

What is most striking is that you can these days predict which drugs HIV is resistant to by sequencing the virus from each individual patient. This feat alone should be impossible if HIV didn't exist, not least because why would the same mutations always appear with the same drug-resistances? People with HIV these days can change drugs with the knowledge that their HIV is NOT resistant to the new one, whereas in the old days it was mostly trial and error. You can correlate drug resistances to treatment success or failure - again, this makes no sense if the virus is meaningless and the drugs non-specific. This simple, common practise every day in HIV clinics all over the world, disproves the dissident views on so many counts.

Not least the views of this guy, apparently the closest thing they have on the forum to a scientist. I wonder what he would think of Aciclovir acting against herpes viruses....


Blogger Brad said...

Hi there,

I wasn't sure if you had come across this article yet. It's relevent to your subject matter, so I wanted to share it with you:

Mother who denied Aids link faces police investigation after death of daughter


4:56 PM  
Blogger Bennett said...

Oh dear - this is actually kind of sad. Most dissidents and orthodoxy alike know of Christine Maggoire and the recent death of her daughter. This is the first I've heard of any definitive diagnosis about her death. You can tell I've been out of the loop recently..

I dunno exactly what they've called "HIV related pneumonia". If it's something like CMV or PCP then I'd have to, unfortunately, agree with that label. However kids can and do get other pneumonias like streptococcal. Right now no-one seems to have the facts to hand, except the coroner, and he's not talking.

Thanks for the link.


7:51 PM  
Blogger Bennett said...

Hi again Que.

I'm not saying that AZT is perfect - far from it, it is probably the second worst anti-HIV drug. I find it amusing that no-one really comments on the worst!

In the same vein, one can defend AZT using the same dissident literature - many if not all of the papers that state that AZT can kill cells also show that AZT can, at far lower concentrations, stop viral replication.

My point is not that AZT it perfect, but if you're going to criticise it then at least have some solid evidence. The stuff you present, that of mitochondrial toxicity, fits with all the evidence. Most neatly it is also interesting to note that the mitochondrial DNA polymerase (which is different from the cellular DNA polymerase) is similar to HIV reverse-transcriptase in several respects. The Perth Group even allege that Montagnier confused it with RT in his early work on HIV. It is not surprisingly in molecular terms that AZT, the first "selective" reverse transcriptase inhibitor, cross-reacts with this enzyme.

Duesberg simply states that AZT causes AIDS, which is ludicrous and makes no sense at all. There is certainly no evidence for that!

10:04 AM  
Blogger Trent McBride said...

Dr. Bennett:

Your email is posted here som I am leaving this in the comments. I have posted a rebuttal of the refutation of the ME in the pediatric AIDS case mentioned above. It is here:

I have posted an update of it here:

In the update I have linked to a paper you wrote for Orac at "Respectful Insolence" that I am hosting on my group blog. I understand you have given permission to do so, right?

Anyway, stop by and feel free to add your comments.

1:32 PM  
Blogger Bennett said...

Thanks Trent, I'll add a new post here with all the relevant links :o)


2:20 PM  
Blogger Bennett said...

Hi Mark,

It's a complete fabrication that AZT was shelved because of toxicity. The myth originated from Duesberg's book, in which he states that AZT "must have" been shelved due to toxicity, because in his mind AZT was an indiscriminate DNA chain terminator.

In point of fact, AZT was shelved because of sheer lack of activity in laboratory and mouse models. It wasn't toxic ENOUGH to kill the tumors and was shelved. Duesberg's error is in not appreciating that AZT won't terminate a growing DNA chain until it is bound to the DNA polymerase enzyme and added to the chain. AZT quite simply doesn't bind very well to cellular DNA polymerases, but does bind well to viral reverse transcriptase. As such, it doesn't matter whether or not AZT is around our own DNA, as without attaching to the DNA polymerase it can't be inserted into a growing DNA chain.

I'm afraid your comment has to be turned around completely - most dissidents simply aren't aware that AZT was shelved due to a lack of efficacy (toxicity) and that the myth originated from a very simple misunderstanding.

Ironically enough this story is detailed on a dissident website, in an exchange between David Crowe and Dr Richard Beltz, who invented AZT. I wrote about it long ago on this blog.

AZT - Not toxic enough

11:23 AM  

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