AIDS: Science at a Crossroads

AIDS: SCIENCE AT A CROSSROADS
1. THE CHANGING PICTURE
1995: Time to go back to basics
AIDS research is at a crossroads. More has been learnt in a short time about AIDS than about almost
any other disease. Yet the unanswered questions are among the most important. For example, why do
some people with HIV remain healthy for many years while others rapidly develop disease? Why are
effective drugs so elusive? Does the immune system put up an effective defence against the virus at any
stage before it is destroyed and, if it does, can it be strengthened? So far, research has focused mainly
on trying to find a cure for AIDS, and a vaccine against HIV. Now, scientists are concentrating again
on the basic unanswered questions.
In May last year, the late Dr Bernie Fields, a leading molecular US biologist at Harvard Medical School
in Boston, wrote in the journal Nature that it was time to rethink the strategy to concentrate more on
basic science, such as learning how the disease damages the immune system, and less on the narrow
pursuit of vaccines and therapies. "The focus on drugs and vaccines made sense a decade ago, but it is
time to acknowledge that our best hunches have not paid off and are not likely to do so," he argued.
In the past 12 months, a number of AIDS research organisations have been rethinking their approach.
Speaking at the Tenth International Conference on AIDS in Yokohama, Japan, in August 1994, Dr
William Paul, an immunologist and the new director of the US government's giant Office of AIDS
Research (OAR), said he believed scientists were "at a turningpoint in the history of the disease".
He believed that "the current inadequacy of treatments for HIV infection and the absence of a vaccine
to protect the uninfected are largely due to the wide gaps in our understanding of the [underlying
disease process].... If we do not provide innovative scientists with the resources and opportunities to
attack the basic unsolved problems related to AIDS and HIV, we may find that a decade from now, we
are no further along in our struggle."
The OAR has overhauled the US National Institutes of Health's entire AIDS research programme -
whose budget is US$ 1.3 billion - to devote more resources to basic science and fewer to clinical trials.
This return to basic research is leading some teams of researchers to examine in detail what happens
when the virus infects people. For example, Dr David Ho and his colleagues at the Aaron Diamond
AIDS Research Center in New York, US, have shown in research published by the scientific journal
Nature in January this year, that, even when people have no symptoms of disease, the virus in their
body is rapidlyreproducing itself in large numbers. Each new virus particle stimulates the production
of certain vital defence cells known as CD4 T cells. The researchers believe that this creates a rapid
turnover of defence cells which then become catastrophically depleted, making the person vulnerable
to other infections.
Another example is the renewed interest in an important group of defence cells known as dendritic
cells. In separate studies, researchers have analysed the effects of the virus on these cells. Dendritic
cells act as "agents of introduction" in the immune system, bringing foreign proteins that enter the
body, such as proteins from infectious agents, to meet the other defence cells and stimulating them to
respond. As the first line of defence, these cells may be vital in protecting the body from infection. But
some researchers have suggested that HIV destroys the normal function of dendritic cells, leading to a
domino-like collapse of the rest of the immune system.
Funding under threat

While research into AIDS has reached a turning point, efforts to control and prevent the disease are also
facing a crisis - this time for political and economic reasons. In the North, political commitment to
tackling AIDS may be faltering This is despite evidence that preventing HIV infection is among the
most cost-effective ways to protect the health of populations (1) and despite the urgency of the problem.

Panos Briefing: AIDS: SCIENCE AT A CROSSROADS 2