COVER

The pursuit of a cure

PAT OHLENDORF August 12 1985
COVER

The pursuit of a cure

PAT OHLENDORF August 12 1985

The pursuit of a cure

COVER

Gilmore, colleague Roger LeBlanc

AIDS invariably kills. Each year the number of victims suffering from acquired immune deficiency syndrome doubles, and the plague has spread far beyond the homosexual community where doctors diagnosed the first cases in 1981. Scientists are searching for ways to combat AIDS but the prognosis for patients is no better than it was four years ago: most will die within three years of contracting the condition. There is still no effective vaccine—or even effective treatment— against the AIDS virus. And the most recent discoveries, while producing important new insights, are chilling. Last March scientists at the National Institutes of Health (NIH) in Bathesda, Md., discovered that AIDS, which depresses the body’s immune system weakening its ability to resist infection, also attacks and kills brain cells. And last month U.S. researchers learned that AIDS viral cells reproduce faster than any other known virus. Concluded William Haseltine, a molecular biologist at Harvard University: “At this point, in the battle between man and microbe we are definitely losing.”

Researchers and clinicians now have only two ways of attacking AIDS: by attempting to kill the virus—or at least stopping it from reproducing; and by strengthening the patient’s ravaged immune system, HPA-23, a substance developed at the Pasteur Institute in Paris, has received widespread attention since actor Rock Hudson flew there in the hope that the antiviral drug would help his condition. But it is only one of several similar compounds, including Suramin, which was used as long ago as 1920 to arrest African sleeping sickness. Those drugs have shown some promise in animal research but so far the results obtained after tests on humans have been inconclusive. NIH scientist Robert Gallo, co-discoverer of the AIDS virus, declared that faith in HPA-23 might prove to be unfounded: “I am a little put off by the publicity centred on one compound which I would not call very outstanding.”

In fact, the aim of many clinical researchers is to determine how well current antiviral drugs—none of which is commercially available—react on different patients. Gallo’s group is investigating Suramin, and a group of Montreal physicians also wants to begin testing that compound, as well as Foscarnet. Almost everyone involved with those drugs — researchers,doctors or even representatives of the pharmaceutical firms producing the substances—say that it is far too early to gauge their effectiveness. Said Dr. Roger Fontaine, medical director of the g French firm that proJ duces HPA-23: “We think * “ it may have some influ-

ence on the virus that causes AIDS but we are far from sure that we have a drug to cure it.” Added Dr. Norbert Gilmore, a Montreal immunologist and chairman of the National Advisory Committee on AIDS: “Some of these substances clearly stop the virus from replicating, at least

while the drug is administered. But that may not mean a cure.” Once patients stop taking drugs the virus renews its rapid proliferation. As well, antiviral treatments often produce such serious side effects as liver damage and loss of blood-clotting ability.

Unabated: Most scientists trying

to defeat AIDS by building up the body’s immune system with such drugs as interferon and interleukin have failed. The virus continues replicating unabated despite the treatments. Even radical

attempts to replace, or at least build up, the body’s failed immune system through bone marrow and thymus gland transplants have been unsuccessful because the virus simply kills the new Thelper cells—white blood cells that direct the body’s resistance to infection. Declared Donald Abrams, assistant director of the San Francisco General Hospital’s AIDS clinic: “Ultimately, we will probably need a combination of both therapies.” And physicians still do not know which combination of antiviral and immune system builders would best help AIDS victims. Indeed, Gilmore’s description of AIDS treatment at Montreal’s Royal Victoria Hospital could be applied to any AIDS clinic in the world. Said Gilmore: “Most of the work we do is counselling.”

At the same time, there does not ap-

pear to be any imminent breakthrough in finding an effective vaccine to prevent AIDS. In fact, researchers do not know whether it will ever be possible to create a vaccine, because the virus —called HTLV-iii in North America and LAV in France—might be mutating, or changing its characteristics, so rapidly that it could prove to be an elusive target. And if it is possible, a workable vaccine would first have to be tested thoroughly. As a result, cautioned molecular biologist Flossie Wong-Staal, a member of Dr. Gallo’s team, such a vaccine might not be ready for the public for “a couple of years.” But by that time nearly 50,000 more Americans and 1,200 more Canadians will have AIDS, and 25,000 North Americans will have died from the disease.

Register: AIDS is such a new phenomenon that even present methods of diagnosis are sometimes inadequate. A small and still-unknown percentage of people infected by AIDS show negative results when their blood is tested for the condition. The reason: the current tests used to detect the disease measure antibodies that the body manufactures to fight the virus; those victims may have so many more AIDS virus cells than antibodies that the antibodies t simply do not register on o the test. As well, a test □ that could detect the vi| rus rather than the body’s reaction to the virus has still not been developed. Said WongStaal: “It is like looking for a needle in a haystack. If you take tissue from any given person, only one in 1,000—or even one in 10,000—cells will be infected by the virus.”

Still, scientific work is continuing at a feverish pace in North American and European laboratories to understand the AIDS virus thoroughly. Without that knowledge, searches for a vaccine and for effective treatments cannot succeed. So far, researchers have determined that the virus is made up of six genes, and they have learned the functions of only four of them. One of them is highly unusual. The tiny gene triggers the virus to reproduce at an incredible speed. Said Haseltine: “We can now explain why the AIDS virus holds the world’s record. It replicates 10 to 100 times faster than any other we know about—it’s really a

heavyweight.” That not only demonstrates how rapidly the virus may be mutating—because, said Haseltine, “rapid replication means more mistakes in copying genetic instructions”—but it also suggested that only a tiny amount of the virus may be needed to infect a new victim.

But Wong-Staal, for one, still says that finding an effective vaccine may be possible. Added the researcher: “We should not play up the negative implications of this until we have actually tried the vaccine experiments.” Haseltine even holds out the prospect of “using the nastiness of the virus against itself” —using the newly discovered gene to trigger rapid manufacture of substances to treat or prevent AIDS.

AIDS also has a powerful ability to kill brain cells. Doctors initially noticed that some victims were depressed, had trouble grasping new concepts or were behaving strangely. Some physicians attributed those symptoms to the shock of adjusting to the death sentence that AIDS imposes and others said that the changes were caused by brain tumors. But Gallo’s researchers made a further discovery when they dissected brain tissue taken from 15 patients who had died. In one-third of the cases they found that the virus had directly attacked the brain cells. In fact, the brains of young children who die of AIDS are sometimes onethird smaller than brains of healthy children at the same age, indicating that the AIDS virus either arrests brain development or destroys cerebral tissue. But for most adult AIDS victims, brain disease is not a major concern. They are aware that they are much more likely to succumb to secondary infections of an especially virulent pneumonia, Kaposi’s sarcoma or cancer tumors long before the virus causes fatal brain disease.

Concern: Some doctors—increasingly discouraged as they helplessly watch patients die—say that more research is needed on the secondary infections that actually cause death. The concern expressed by Constance Wofsy, specialist in infectious diseases and a co-director of the San Francisco General Hospital’s AIDS clinic, underlines the hopelessness many clinicians feel in the face of the mounting AIDS epidemic: “We just don’t have enough drugs to treat conditions like the pneumonia, Kaposi’s or the cytomegalovirus that leads to blindness. Of course the patients will die anyway, but we should try harder to increase the amount of time they have left, even if it is only a few months. We should be concentrating on improving the quality of the little life remaining to those patients, to see that they are reasonably comfortable, and that they are able to die with dignity.”

-PAT OHLENDORF in Toronto