Big hunt on for A.I.D.S. agent

Press, 13 October 1983, Page 27

Big hunt on for A.I.D.S. agent

The profound disorder of the body’s normal immune defences against disease, A.I.D.S. has now affected more than 2000 people in the United States alone. Millions of dollars and a lot of effort are being poured into research on A.I.D.S.

To the layman, it must seem extraordinary that scientists still do not know even what causes the disorder. After all, when Legionnaires’ disease hit the headlines in 1976, it took less than a year to track down the culprit, a bacterium, responsible for it. Cases of A.I.D.S. in America were first recognised as a big health problem in 1981. Why has the agent causing it proved so elusive?

To understand, consider how scientists go about searching for the cause of any apparently new disease. The first step is to look hard at the disease itself: its symptoms, course of development and the pattern of its incidence. That alone may tell you what kind of agent is probably involved: e.g. a bacterium, a virus or even a fungus. It can also tell you where to look for it. Legionnaire’s disease, for example, affected the lung tissue of victims.

It is clear that the agent causing A.I.D.S. can be transmitted via blood and certain other body fluids.

It is also clear that the agent targets particular cells in these fluids: socalled T-cells involved in the body’s immune system.

Given the characteristics of Legionnaire’s disease, medical sleuths were pretty sure they were looking for a bacterium — and one probably very like other known pneumonia-causing bacteria.

Given the characteristics of A.1.D.5., most researchers reckon that the causative agent is a virus (or possibly an even simpler organism known as a viroid) — and presumably one that resembles other viruses that can suppress the immune system.

One candidate as the A.I.D.S. agent is the human T-cell leukaemia-lymphoma virus (HTLV) which is implicated in certain rare cancers and which targets the same T-cells involved in

A.I.D.S. A number of screening tests exist that can tell you whether your initial hunch about whether you are dealing with a bacterium or a virus looks correct.

For example, a filter fine enough to catch the smallest bacterium (roughly 0.4 microns, or millionths of a metre, in diameter) will not catch a virus: even the relatively large flu virus measures only 0.08 microns across.

A look down an ordinary microscope may pick up larger infective agents. A high-powered electron microscope may find viral particles — if the virus is replicating. With luck, such tests may even tell you which class of bacterium or virus or whatever you are after. For instance, certain standard stains (about 10 types) are taken up only by different classes of bacterium. Similarly, different classes of virus tend to grow in different tissue culture mediums.

Beyond these relatively non-specific tests lies a battery of “identikits” tests capable of spotting specific agents. Essentially, these all rely on using probes that can recognise (and latch on to) known agents. The probe may be an antibody — e.g. in the infected blood of a patient — raised against a specific molecular marker on the surface of a virus. Or the probe may be a match of the genetic (DNA or RNA) heart of the agent. If the agent you are looking for is utterly new, these probes may not react with it. But, with any luck, your agent may be a variant on an old theme — e.g. a more virulent strain — and share characteristics with a more familiar strain.

You may be able to refine your probes so that they will recognise these shared characteristics. This is now being tried with A.I.D.S. and the HTLV virus.

In practice, there are all sorts of problems — not least, getting enough material on which to work. No one test is conclusive and many overlap.

In the case of A.1.D.5., these problems are compounded by the messy

nature of the disorder. The A.I.D.S. agent ' wreaks its havoc indirectly. Because it suppresses the immune defences of its victim, it opens the door to many other disease-causing agents: patients die not of A.I.D.S. itself but the “opportunistic” infections it brings in its train. So one headache is to separate out the A.I.D.S. agent from all the others. One approach is to look at patients at an early stage of the disease. Other problems arise from the nature of the presumed quarry. Viruses (let alone viroids) are elusive partly because they are tiny. And the A.I.D.S. agent may be particularly hard to get at, especially in adequate quantities. It may be one of those viruses that stitches its own genes into those of the cells it infects.

So far, nearly all of the tests carried out to determine the cause of A.I.D.S. have proved inconclusive. Indeed, only antibody tests have uncovered anything of potential significance. In several hundred samples of blood serum, some 30 per cent of the samples from A.I.D.S. patients have contained antibodies to HTLV virus compared with 5 per cent of those from healthy homosexual men. So scientists are now trying different approaches. They are looking at tissues from A.I.D.S. patients that are not normally involved in the disorder to see what they might harbour. They are tagging unusual viruses with fluorescent markers to see whether these will show up under a microscope; They are also trying to find an animal model of A.I.D.S. Some researchers are trying to grow infected Tcells in culture and then to use promoters aimed at stimulating the replication of the HTLV virus. Others are mixing infected cells with healthy ones and then using promoters to try to trigger viral replication in the initially healthy cells.

The outlook? Scientists are betting that the A.I.D.S. agent will be found — if only because it is spreading so fast that there are plenty of patients to work with. — Copyright the “Economist.”