NOVA Online | Surviving AIDS | Search for a Vaccine (2)

Search for a Vaccine
part 2 | back to part 1

NOVA: Since everybody's genetic background is different and their immune systems react differently, and since there are a million variations of H.I.V. out there, is it possible that we won't be able to find a single overarching vaccine?

Baltimore: We may never be able to make a vaccine. But I'm hopeful. We have to be optimistic at this point, because we don't have enough reason to be anything else.

NOVA: What about the idea of a vaccine that changes the course of the disease rather than preventing it?

Baltimore: I believe that whatever vaccine we come up with will change the course of the disease without preventing infection completely. In fact, all vaccines work that way. The polio vaccine doesn't prevent infection with polio; it prevents polio getting into the nervous system. So it prevents disease, not infection, and that's true of all vaccines. It means that people who get infected with H.I.V. may be infected in a lifelong way. We're infected with lots of viruses for our lives; they just don't cause the kind of problem that H.I.V. does.

NOVA: But if you do get infected, and you don't get sick, the possibility is always there that it could pop up, right?

This viral load assay measures the amount of virus in a patient's blood with a yellow indicator. The third column from the left is a patient with acute HIV; the fourth, long-term non-progressor Bob Massie.

Baltimore: It could get worse. But the long-term non-progressors suggest that virus can be maintained at a low level for 20 years anyway. And that gives us hope that if we can suppress the initial response to the virus, then maybe the body can carry that forward for a very long time.

NOVA: How optimistic are you about being able to rescue the immune system in the early stages of H.I.V. infection?

Baltimore: In the early stages, the immune system is not particularly devastated. So if we can suppress the virus I think the immune system will pop back. There is pretty good evidence now that it does come back and can be strong. It's people who have been infected for a long time whose immune system is really devastated. The question is: Can their immune systems be reconstituted to the point where they become immune-responsive to new pathogens, or where they can handle the environment around them?

It's impressive how healthy people are who have been infected for a long time but in whom the virus is suppressed. Those people don't get opportunistic infections, they don't get a whole series of things you might worry about. So maybe enough immune response comes back to make them able to fight off the common problems.

By studying the immune response of John Ceravsky, one of the first HIV patients to volunteer to stop therapy, scientists hope to find a cure for those infected with HIV.

NOVA: Over the past ten years of this epidemic, there have been moments of great hope associated with a lot of hype, and then it turns out often that it's not as great as we thought. Can you talk a bit about that cycle and where we might be in it at this moment?

Baltimore: You're now referring more to treatment of H.I.V. than prevention. We are in a position now where H.I.V. is a treatable disease. It's like many other diseases: not everybody responds well to the treatment, not everybody has their H.I.V. suppressed completely, not everybody can live with it for a very long time. That's no different than the treatment for a lot of other diseases. But enough people are suppressed in their virus load and are able to lead relatively complete lives that you have to say H.I.V. is a treatable disease.

That's a major change over what was true just a couple of years ago. We've just got to get better at it. We've got to cut down the number of pills people have to take, make the regimen easier to follow, cut down the side effects, and design better and better drugs. But we have a platform now that we can build on, and it's only going to get better from here.

NOVA: Where does the basic research on H.I.V. stand at this moment?

Combinations of antiviral drugs—the AIDS cocktails—can prolong life for many patients.

Baltimore: It's interesting. If you look at H.I.V. in terms of the amount of genetic material that it has, it's a small virus—10,000 nucleotides roughly. That's nothing. In the great scheme of our genome, that's just throwaway information. Now, H.I.V. has packed into that 10,000 nucleotides an enormous amount of biological cunning, much of which we had never seen before in a virus. So we have had to learn about all those bits and pieces—how they work, what they do—and without sufficient background to be able to say, "That's another one of X or another one of Y." This is the first one we've ever seen of this kind, in many different ways.

So the basic research effort on H.I.V. has been a very tough problem that has ramified into many areas of molecular biology, of immunology, and it's still going on. We still do not understand the details of most of H.I.V.'s very subtle genes.

On the other hand, we've learned a tremendous amount along the way. We've learned a lot of new biology, and a lot of people are excited by it. The very best people in the country today are aware of the opportunity that H.I.V. provides to do really good biology. H.I.V. has definitely pushed the limits of science. It has pushed the limits of chemistry, of cell biology, of understanding transcriptional control, of understanding how genomes work, of integration of genes, just everything.

Finding a vaccine for HIV has pushed the limits of chemistry, cell biology, and genetics. Finding a cure, David Baltimore believes, will require truly innovative thinking.

NOVA: If you had to look ahead five or ten years, what do you think would be the most likely outcome of all this research?

Baltimore: I don't know what's likely, but I can tell you what I hope for. I hope that we'll have a vaccine and that within what has to be measured in a decade or more we'll find a way to stimulate the immune system so that when people get infected, they suppress H.I.V. rather than allowing it to flourish. But for that to happen, I really think it will have to be based on some new thinking about viruses.

Illustration: (7) Courtesy of Dr. José Assouline, University of Iowa College of Medicine.

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