Mar 21, 2008


Because it isn't published yet, I can't say much about the work I did last summer on an HIV vaccine. What I can say is that the work wasn't particularly glamorous. I spent a lot of long hours mixing and measuring tiny amounts of clear liquid in tiny plastic tubes, which isn't quite as exciting as rocket science, but hey - that's bioengineering. Things that bioengineers think are exciting are generally about as thrilling as watching paint dry.

But damn, if it works... Imagine how it would change the world. Just thinking of it gives me the shivers.

HIV is a tricky monster. It attacks CD4+ T cells. Those helper T cells are supposed to activate B cells, which then produce antibodies, which bind to the virus, causing them to be endocytosed by macrophages. So if you don't have any T cells, you don't have any antibodies, which means that your specific immune responses are... zilch.

When it enters cells, HIV unpacks its (tiny, efficient, scary) RNA genome, uses an enzyme called reverse transcriptase to translate the RNA in to DNA (all the better to mimic human genes), and then inserts itself in to the human genome. There it lurks for years.

The virus can only replicate if certain transcription factors (molecules which bind the DNA such that transcription to RNA can occur) are present. (For example, in the case of HIV, one of the factors it needs to jump out of the human genome is NF-kappa-B. Sadly, NF-kappa-B is upregulated (produced more) when T cells are activated.) When such a transcription factor comes along, the viral genome is transcribed to RNA and translated to protein unwittingly by the body's machinery. The completed virus assembles, bursts out of the host cells, and goes on to infect again.

It's awful.

HIV is only made trickier by its tendency to mutate extremely quickly. The virus can change significantly within one person, within one month (this is mostly because the virus doesn't package its own proofreading enzymes, so when it transcribes its own genome, it makes a lot of mistakes). Which is part of the reason that no vaccine has been made so far - it's incredibly difficult to fight against a mutating enemy.

Therapy for HIV basically consists of anti-retroviral drugs right now. They work in a number of ways - they can inhibit reverse transcriptase, they can inhibit some of the viral proteins necessary for viron assembly, they can inhibit the protein that allows HIV to insert itself in the human genome, etc - but all of them focus on blocking the virus from doing what it wants to do. This means that all of them are dependent upon the virus not mutating so much that it becomes unrecognizable to the drug - and that's unlikely, given how fast HIV mutates. So lots of people become resistant to treatment, and then there's very little that medicine can do.

Most of my understanding of HIV and AIDS comes from a very scientific perspective. I know a lot about HIV surface proteins. I can go on about immune response. But the epidemic hasn't come too close to my life. It started just before I was born, and by the time I was old enough to know anything about it, it was a pandemic. Friends watched friends waste away. AIDS orphans were suddenly everywhere. The disease reared up from nowhere, ugly as hell.

I've never personally known anybody with HIV or AIDS. I've never even met anybody with HIV or AIDS (that I know of - though I probably have). Sometimes it makes AIDS seem so surreal. I've been hearing about it ever since I can remember, this hellish disease, for which we have no cure. I even forget, sometimes, that the disease is only a couple years older than me. How can it even be real? How can it have changed the world so fast?

Once in a while, I get a flash of understanding. Maybe I read something (like Susan Sontag's "The Way We Live Now" - not for the faint of heart), or overhear something on the T... Today, in a restaurant, just as I was leaving, I heard a group of people make a toast to a man who had died of AIDS. In those moments I'm reminded how blissfully untouched by AIDS my life has been, and how little I really know about it. And how very, very far we have to go before it can be forgotten.

1 comment:

J said...

The magic of BE is what happens in the worlds we cannot see - that's why there's a bit of a dreamer in every one of us bioengineers. I'm working on nanoparticles right now, and I'm willing to admit that watching paint dry or grass grow is more exciting than watching peptides and nanoparticles filtering through a column for an hour. But as you say, the potential for change is enormous, and that's enough to get me to spend a lot of my spring break in lab to keep moving towards that distant goal.

I once had a conversation about HIV with a PI (at Weill Cornell) who was working on it, and he explained how HIV managed to thwart the cell's efforts to chop up RNA with nucleases and to bind blebbing envelopes to the surface to prevent the spread of virus. I think there is no more appropriate term to use than "arms race." I really admire your bravery in joining a fight against this virus. Are you planning on continuing research that addresses HIV in the future?