Saturday, February 16, 2008

ERV vs David Baltimore

This week, The David Baltimore finally came out and said what everyone in HIV research is thinking. Every other day you hear press releases from universities and crappy reporting declaring 'HIV VACCINE IN 2 YEARS!!' (Bossman was 'quoted' in one of those articles last summer). But Baltimore finally got a reporter to just say it:

Attempts to control the virus through antibodies or by boosting the body's immune system have ended in failure.

This has left the vaccine community depressed because they can see no hopeful way of success, Prof Baltimore said.

Yup. HIV vaccines. Epic Fails. I mean epic, with recent trials ending after the vaccine somehow increased HIV infection rates.

HOWEVER Im still pissed at Baltimore, and we would have gotten into a tif over his comments. First of all, the rest of the article is pushing the HIV-gene-therapy therapy the Gates Foundation has been funding.

"In the human you really only have one shot which is to try to change genes in stem cells," said Prof Baltimore, one of the leading experts on the HIV virus.

"So we're trying to do that, to design vectors that can carry genes that will be of therapeutic advantage."

I read about Baltimores strategy last fall in Science, 'Building an HIV-Proof Immune System':
Instructive immunotherapy

At the California Institute of Technology in Pasadena, David Baltimore has teamed up with immunologist Pamela Björkman on an HIV gene-therapy project that he calls "instructive immunotherapy." Rather than bolstering the natural immune response, Baltimore says, "we're instructing the immune system [about] what to make."

This 5-year experiment lives up to its Grand Challenges billing with its focus on inventing virus-fighting antibodies. Gene therapists have paid antibodies little heed because HIV notoriously remains impervious to their attack. "I didn't think we should be giving up on the historically most powerful part of the immune system," says Baltimore. So he and Björkman are attempting to construct an antibody against HIV that's far more powerful than anything naturally produced by the immune system. Baltimore and co-workers then want to use an HIV-based vector to transduce the gene for this antibody into immune stem cells.

What I understand of that endeavor is that you take out someones pre-B-cells, alter them to produce neutralizing antibodies, and insert them back into the patient before they are infected with HIV.

Yeah. Thats a workable solution for AFRICA. Common. Common. What the hell.

Id also say that the only HIV vaccine researchers who are 'depressed' are the ones that have been failing and are currently out of ideas. I might be discouraged, but Im not 'depressed'. From my appearance on IGs show last week:
IG-- Do you think we will ever have a cure for HIV?

ERV-- Im not sure about a 'cure'. I would be happy with reducing it to a herpes level, where you have to be on drugs, it sucks, but its not going to kill you. Its not going to bankrupt you, trying to get drugs. Im optimistic about a vaccine for it, though! Im not optimistic about current vaccine trials, but Im optimistic about my research and its potential to lead to a workable vaccine target.
Here is why I think others might be 'depressed' (*warning* following info is from a bratty student bitching at people who have been involved in HIV research since before she was born). Remember quasispecies? How its like a big cloud floating in sequence-space? Current vaccine trials have been like shooting V2s into the cloud. The cloud doesnt care.

My research is based on the hypothesis that the cloud is... um, a cloud. Its a smokescreen hiding the real targets for a vaccine. We have been so intimidated by the cloud that we havent stopped to think that its not the cloud we need to worry about-- there are molecular determinants to sexual transmission. Focus on the viruses with the 'transmission' characteristics. Ignore the rest of the cloud. Got yourself a workable vaccine.

The 'vaccine community' might be depressed, Baltimore, but the basic virologists arent.


Or I might be setting up an epic fail myself.


Anonymous said...

Maybe sometimes it just takes someone to have that Eureka moment. It'll come. The fundies will probably try and stop the vaccine from being available when it comes anyway... (like the HPV one)

Tyler DiPietro said...

"Yeah. Thats a workable solution for AFRICA. Common. Common. What the hell.

It may not be a workable solution economically for poorer countries, but it's still worth persuing if it has promise for preventing infection. We have a saying in computer science, originating from Don Knuth: "premature optimization is the root of all evil." Solve the problem first, then sort out the scaling and efficiency issues.

Ethan Obie said...

I do HIV research on the public health side (actually its more like evolutionary biology of HIV applied to public health, which is do bad ass that it makes me wince). Anyway, your comments are spot on in my opinion. I'm glad that Baltimore is injected some much needed skepticism into the reportage on HIV vaccines. And, I totally agree that uber-high-tech solutions are not going to play well on the global stage (although we should still pursue them). Of course (as an epidemiologist) I think the problem is our misunderstanding of the population-level sexual dynamics that makes current prevention schemes ineffective.

Lledowyn said...

Hopefully, you're not setting yourself up for an Epic Fail, but even if you are, your research will add to the current body of knowledge of HIV which will eventually lead to either a cure, or an effective vaccine. I really do believe that we will eventually beat this insidious virus, it just sucks that it's not the kind of thing that will happen any time soon. :(

Brian G. said...

Thanks for explaining this, Abbie. I was a bit upset by the story and needed some clarification, which is why I emailed you about it.

Unsympathetic reader said...

By all means, let's try introducing modified genes into a patient's stem cells in a manner that doesn't cause cancer because the integration site wasn't sufficiently specific. Lotsa luck...

Art said...

That seemed an intelligent and realistic attitude, Abbie. You didn't ravage Baltimore, but explained your honest differences. And, of course, anyone could be right at this point (except IDiots like Behe).

During a laparotomy for Hodgkins lymphoma in 1984, I was transfused with 8 units from San Francisco's notorious Irwin Memorial blood bank.

Naturally, once I heard of this and knew of the way HIV was spreading from that blood bank, I wanted to be tested for HIV. I turned up negative, thank goodness. But at that time, I had a few interesting conversations with my oncologist, at South San Francisco Kaiser, Dr. Killbridge.

He told me that he felt (in 1984, remember) that AIDS might turn out to be the hardest disease ever to conquer. It was already known that the virus evolved defenses at an incredible pace. But Killbridge also felt that the research it would be a boon to medicine in general. Before the AIDS epidemic, there were few if any antivirals. Now, largely thanks to HIV researchers, antivirals are becoming common.

We know enormously more now about viruses than we did in 1984.

I admire you viral researchers. You've got a tough enemy. It's a battle of human intelligence against nature's most potent secret weapon, evolution. I know we'll get the best results that nature allows us to seize.

-- HalfMooner

Israel Barrantes said...

Don't get too personal, Abby. Famous people like Baltimore sometimes need to promise fake stuff to get more press coverage (i.e., to get more grants). You know what I mean.

Tatarize said...

What's so hard about that? We simply extract a skin cell, dedifferenciate it with some unknown process that won't end up giving you cancer, increase the length of the telomeres (might as well become younger too/help the stem cells take over too) replace a few genes with two mutated version of CCR5 (immunity to HIV), splice in the ability to synthesize your own vitamin C too. A pet project or two just shove those into the DNA too. Make a large line of stem cells and reinsert them into an individual to take over their body and replace their previous genetic code, as their old cells wear out.

What could possibly go wrong?

Che said...

Excuse my ignorance, but has humanity developed a succesful vaccine against any retrovirus?

Rich Hughes said...

Humanity hasn't, but we've evolved through a few, as it were. Traces of ERV's are bout 8% of our genome.