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