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Hollywood producer Harvey Weinstein is reportedly in talks with Gorillaz co-creators Damon Albarn (of Blur fame) and Jamie Hewlett (of Tank Girl fame) to make a movie based on the animated band. Quoth Albarn, "We're going to try and do something which makes the world not just think of Wallace and Gromit when they think of animation." Will the British lead the way in (English-language) animation for mature tastes, just as they did for comic books? Regardless, now would be a good time to generate some buzz if you want to see this happen.

While perusing the reviews for the Quantum Leap, Season 2 DVDs on Netflix, I discovered every one contained some variation of the following statement: "Most of the period music has been replaced by some horrible generic music! " That's right, the RIAA has been demanding heavy royalties on music featured on or even played in the background of older TV shows that want to be released on DVD, forcing the TV studios to either pay up, edit, or not be released at all. Shows like WKRP in Cincinnati are priced right out of the market. Nice work fellas.

Up until recently, the only method for dealing with viral illness (aside from just weathering it) has been vaccination. And essentially, a vaccine is just a sort of advance warning to the body's immune system to let it know what to be ready for in the future. Within your immune system is the potential to identify and filter out trillions of different antigens (foreign substances and proteins), given enough time to identify and bring them to readiness. Even without a vaccine most viral illnesses go away on their own as our immune systems catch on the normal way. We have vaccines and/or successful vaccine-development programs for just about every major viral infection known to man - except HIV. After over twenty years of vaccine research, not one has proven itself even partially effective.

Presumably the main obstacle is HIV's pronounced tendency to mutate into new, unrecognized forms. Furthermore, only a handful of viral proteins are actually exposed where the immune system can detect them and the virus replicates at an extremely high rate, essentially giving us a narrow window on a fast moving target. Perhaps most troublingly HIV attacks the very immune systems necessary to defend against it. The full dynamics of neither HIV's attack nor the immune systems defense is well understood. All we know is that no matter what antigen you try to prepare the immune system with, no matter how much time it has to find the proper antibodies on its own, HIV has proven it can outmaneuver our bodies defenses for years and kill us in the end. An increasingly aired view among researchers is that, for the most part, the human immune system is simply incapable of keeping up with HIV's incredible adaptivity.

Nevertheless, there are at least three somewhat unconventional vaccine approaches that may yet bear fruit.

The first are the DNA vaccines. Rather than using live or killed virus, naked viral DNA is blasted into your cells so that they generate viral proteins and thus stimulate the immune system. While this is a novel system that bypasses many of the difficulties of other vaccination techniques and may thus be widely applicable, there is ample reason to think that it will offer no solution to HIV's ability to adapt. Proponents of this novel technique nevertheless remain cautiously optimistic.

The second is not actually a preventative vaccine at all. It is perhaps better described as a therapeutic vaccination technique, which appears to be capable of reducing viral load to a tenth of its normal levels. Essentially it is a way of helping the immune system do its normal job. Dendritic cells are isolated from the patient, then exposed to killed HIV virions purified from the patients own blood. These cells are now primed to specifically target the HIV virions affecting the patient, and a reinjected, where they mount a massive sustained attack on the virus. The treatment is believed to be effective for about a year, has no side effects apart from swollen lymph nodes, and overall costs less than present drug treatments, which it can be combined with thus enhancing the treatment. But what it definitely is not is preventative.

The third treatment may have actual potential as a preventative vaccine. Again, the biggest problem with HIV is its ability to change - but therefore, if you can find a part of the virus which does not change and target that, it would have no room to maneuver. Researchers in france believe they have discovered just that, and developed a vaccination treatment which appears to work in the lab at the cellular level at least. Furthermore, the vaccine is easy to manufacture and quite cheap. Trouble is, if we could make a vaccine that works then why can't your own body stumble onto that response on it's own? Indeed, in the original paper announcing this research is a table indicating at least some AIDS patients already possess this activity. Nevertheless, it is worth at least trials in vivo.

The most immediate treatment for HIV happens to belong in what may be regarded as the simplest and so far only partially effective block on HIV: drugs.

Drugs are chemical compounds which inhibit, enhance, or otherwise interfere with the biochemical processes involved in disease and its defense. Most of the time they are rather small and often completely unnatural. Drugs have long been the method of choice when the body's own systems go awry due to injury, poisoning, or genetic disease, allowing us to intelligently if inelegantly regulate our own biochemical processes with natural plant and fungal compounds or more modern and powerful synthetics. More recently the class of drugs known as antibiotics revolutionized medicine by allowing us to specifically interfere with the biochemical processes at work in infectious bacteria, which are rather different from those of our own. Bacterial infections used to be the greatest danger of pre-modern times, but now rarely cause great worry.

What drugs were not very good for were viruses, which make extensive use of our normal cellular machinery to propogate themselves and have few biochemical targets of opportunity, none of them common. But when HIV failed to yield to vaccines, drugs became our second focus. Modern drug cocktails have become quite effective at keeping the virus in check, but HIV has a pronounced tendency to evolve around them.

The latest salvo in the battle is a class of drugs known as DAPYs, the power of which is twofold. Firstly, they are designed to specifically inhibit reverse transcriptase, a viral enzyme which copies the viral blueprint into our own DNA. In other words, DAPYs prevent our cells from actually becoming infected (most of the other drugs interfere with the replication within the already infected cell). Secondly, it is much more difficult for reverse transcriptase to mutate resistance to these compounds because the DAPYs under consideration are flexible, like a key that can shape itself to fit the lock. Putting it all together means you have a single drug that works as well as or better than today's complicated five-drug cocktails, and it is easy to manufacture and apparently has no significant side effects as well.

So far three DAPYs are working their way through FDA testing, with the latest - R278474, also known as ripilvirine - being the most promising. Its creators are highly optimistic, even going so far as to call it a "magic bullet that stops AIDS in its tracks." But is it a cure? The answer is probably no. In order to completely cure someone of HIV, four things would need to happen simultaneously and complementarily:

1) New infections of cells must be prevented
2) Virions must be cleared from the body
3) Virion-producing actively infected cells must be eliminated, or otherwise permanently prevented from producing virions.
4) Latently infected cells must be activated, so that they may be eliminated as in (3), or otherwise permanently prevented from producing virions.

DAPYs only prevent new infections (1). The immune system and time can handle (2) through humoral immunity and (3) through cellular and humoral immunity and cell death. But (4) is the kicker. Studies indicate HIV could stay hidden inside cells for up to 60 years. During that whole period of time, latent infections could be spontaneously activating and attempting to re-establish an acute infection - which would be largely undetectable like HIV infections now. Even if DAPYs work perfectly and no resistance was ever evolved to them, you'd have to consistently take them for the rest of your life in order to prevent you from becoming infectious again.

So although DAPYs might offer a way for people to avoid developing AIDS entirely, it is no cure for the underlying HIV infection. And if people no longer take AIDS seriously because totally effective treatments are available, they will likely stop taking precautions and undiagnosed infections will spread like wildfire through the population. All well and good if your infection is identified and you don't mind taking drugs for the rest of your life... and assuming HIV doesn't evolve resistance to DAPYs. We'd probably be better off putting it in the water before then.

There is some hope. The mechanisms by which HIV becomes latent, and the means to pull infected cells out of their latent state and thus flush out the viral reservoirs are being studied. But that research is far from yeilding any practical applications. And even if we did have them, how can we be sure the virus has been completely eliminated? In the meantime, DAPYs will be proving themselves in the real world within the next few years.

In the interest of this series of HIV entries I feel I should point out a few basic facts. There are essentially seven major ways of harm to living things:

1) Injury
2) Poisoning
3) Genetic illness
4) Prion infections
5) Viral infections
6) Bacterial infections
7) Parasitic infections

Within each category there are infinite ways to damage, but there are also common strategies for dealing with each. What I want to highlight here is the importance of basic research. A deep understanding the physical, chemical, and biological circumstances which surround these afflictions has allowed huge advances in the treatment of all of them. More importantly, it has been progressively chipping away at the roster of untreatable diseases for which the general strategies do not work.

HIV/AIDS is one such case. Virtually every other virus we have kept at bay has been dealt with the same way: vaccines. Drugs may alleviate symptoms, but there was no substitute for the immune system's ability to seek and destroy viral infections. All a vaccine does is let our immune system know what sort of threats it should be prepared for, so that when they do arrive it is ready to defeat them. Up until now our chief worry was viruses that spread too rapidly upon initial evolution to develop and distribute the vaccine (like SARS or the various flu variants). Generating those vaccines has long been a straightforward if tedious procedure for decades. But attempts to develop a vaccine for HIV in the usual way have all failed, due to its ability to mutate rapidly and attack the immune system itself. This has forced medicine to study the biology of HIV to an unprecedented depth, that we may combat it as we have no other deadly virus before it. All the propositions I will mention in the coming days have relied on this unique effort.