Cover Stories "You Haven't Heard Anything Yet"

By Claudia Wallis

It was A.D. 1348, one year after the bubonic plague, or black death, had begun its devastating rampage through Europe. In a famous medical treatise French Surgeon Guy de Chauliac of Avignon recalled his impressions of the horror around him: "The father did not visit the son nor the son the father. Charity was dead and hope abandoned . . . For self-preservation there was nothing better than to flee the region before becoming infected."

Guy's patients died within five days of falling ill. Cities were decimated in a matter of months. The scourge was so contagious that, according to Guy, "no one could approach or even see a patient without taking the disease." By the time the epidemic subsided a few years later, at least a quarter to a third of all Europeans -- perhaps 25 million people -- had perished.

Today's plague is a very different beast. AIDS works its way through a population slowly, over a period of years and even decades. It also tends to kill slowly, laying waste the immune system so that patients fall prey to a debilitating succession of infections. Unlike the plague of Guy's era, it is spread only through the most intimate forms of human contact: sexual intercourse, childbearing, the sharing of contaminated blood or needles.

Yet as the AIDS death toll climbs and statisticians project its probable course into the next decade, comparisons with history's greatest killers begin to make sense. "If we can't make progress, we face the dreadful prospect of a worldwide death toll in the tens of millions a decade from now," warned Health and Human Services Secretary Otis Bowen at a recent gathering of the National Press Club. Such earlier epidemics as typhus, smallpox and even the black death will "look very pale by comparison," he continued. "You haven't read or heard of anything yet."

The projections, if accurate, would bear him out:

-- Cases of AIDS have been reported in 85 countries, though the World Health Organization suspects that the disease has actually struck as many as 100 nations. WHO officials estimate that between 5 million and 10 million people around the world now carry the AIDS virus, and that as many as 100 million will become infected during the next ten years.

-- In the U.S., more than 30,000 cases have been reported, and another 1.5 million people are thought to be carriers. If the epidemic continues to spread at its current rate, the Centers for Disease Control (CDC) in Atlanta predicts, the total number of cases will reach 270,000 over the next five years, while total AIDS deaths will rise to 179,000. Fearsome as that count is, it falls short of the tolls taken by the influenza epidemic of 1918-19 (500,000 U.S. deaths) and by polio in the mid-'40s to mid-'50s (360,000 cases with 20,000 deaths). But then again, AIDS is still gathering steam.

-- In Africa, as many as 2 million to 5 million may already be infected, and in ten years, predicts Epidemiologist B. Frank Polk, of Johns Hopkins University, "some countries could lose 25% of their population." The loss in terms of the economy and social structure could well equal the black death's ruination of medieval Europe.

-- AIDS is posing an economic threat in the U.S. The cost of caring for victims of the disease, many of whom are denied health insurance, is already estimated to exceed a billion dollars a year. By 1991 AIDS medical bills could total as much as $14 billion annually, according to Health Economist Anne Scitovsky of the Palo Alto (Calif.) Medical Research Foundation, "and that does not begin to address the loss in productivity from the death of people in the prime of life."

-- The prognosis for carriers of the virus seems bleaker than previously imagined. While public health officials first believed that perhaps 10% of those infected would go on to develop AIDS, evidence now suggests that at least 50% of them will progress to the full-blown disease. As more cases are reported, researchers have come to realize that the chances of developing AIDS are greater in the second five years after infection than in the first. "As time goes on," says Dr. James Curran, a top AIDS epidemiologist at the CDC, "only a minority of infected people will remain healthy. I feel less optimistic about a normal life span for any infected person."

But for all the staggering statistics, frightening findings and apocalyptic statements, uncertainties abound. Few experts expect the situation in the U.S. ever to reach the catastrophic proportions evident in Central Africa. While the African epidemic is spreading throughout the general population, in the U.S., it is concentrated among high-risk groups: homosexual and bisexual men and intravenous drug abusers. The proportion of heterosexual cases, however, is increasing at a worrisome rate. For the present the heterosexuals facing the greatest threat are those most likely to consort with infected drug addicts: mainly the inner-city poor, who tend to be black or Hispanic. "Two- thirds of the heterosexual cases now are black and Hispanic, concentrated on the East Coast," says Curran. "I would predict that AIDS would spread fastest in those communities."

The most encouraging difference between AIDS and epidemics of the past is the pace at which medicine is coming to grips with the crisis. "We're talking about a disease that was recognized from a practical point of view only in 1981," says Dr. Samuel Broder, who oversees the development of anti-AIDS drugs at the National Cancer Institute in Bethesda, Md. Since that time, he notes, the cause of AIDS has been discovered, the virus cloned, a blood- screening program implemented and development of a vaccine begun. Possibly most remarkable, the FDA is soon expected to approve the first therapeutic drug: azidothymidine (AZT), manufactured by Burroughs Wellcome.

AZT, which has already been given to more than 3,000 AIDS patients, is a source of optimism to AIDS researchers. "The drug has taught us that it is possible to make significant inroads against the virus," says Broder, "even in patients who are quite advanced." AZT not only prolongs survival, he explains, but produces "clinical improvements: weight gains, increased energy, neurological improvements." It can reverse one of the most disturbing symptoms of advanced AIDS: dementia and loss of mental function.

Unfortunately, AZT is not a cure and has a number of serious drawbacks. It must be taken every four hours around the clock to be effective, and can cause severe bone-marrow damage and anemia in some patients. "It's not an answer, and it's very toxic," says Polk, of Johns Hopkins. "Probably half of our patients on AZT will require weekly or bimonthly blood transfusions."

Perhaps the most promising of the dozens of other AIDS drugs under development is dideoxycytidine (DDC), which belongs to the same category of drugs as AZT. Like AZT, it works by interfering with viral reproduction, but researchers hope it will prove to be less toxic. Hoffmann-La Roche expects to receive a license to manufacture the drug within the next few months.

Doctors generally agree that they will need a two-pronged approach in order to treat AIDS effectively. In addition to eliminating the virus, they must rebuild the patient's ravaged immune system. That may turn out to be the most difficult goal to achieve; researchers have had little success so far with such natural immune boosters as alpha and gamma interferon. Indeed, AIDS therapy may ultimately prove to be most effective in patients whose immune systems are not yet destroyed -- those who show only early symptoms of the disease or perhaps are symptomless carriers. With drugs like AZT, says Broder, "it might be possible to prevent the onset of AIDS. That's a possibility."

Protecting those who have not yet become infected has an equally high priority, and research on vaccines for AIDS is proceeding at an unprecedented pace. Of the many groups at work on a vaccine, Genentech, of South San Francisco, Calif., appears to be one of the furthest along and may begin tests of a prototype vaccine on humans as early as this year. But vaccinemakers face several daunting obstacles. Perhaps the most formidable is the fact that the virus mutates and changes its outer coat so rapidly that no single vaccine is likely to be effective against all strains. Researchers are seeking a section of the viral coat that remains unchanged despite the mutations, hoping to use it as a basis for a vaccine.

Another potential solution is being explored by Dr. Allan Goldstein at George Washington University. Goldstein has found that it is possible to use a protein from the core of the AIDS virus to immunize laboratory animals. This protein, unlike those in the outer coat, does not vary much from one strain of the virus to the next. Says Goldstein: "We think we've overcome the problem of a constantly changing virus." Even if he has, it remains to be shown that this or any other vaccine preparation can actually protect people from infection. Predicts Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases: "It is very unlikely that we will see a vaccine available for widespread use any earlier than the mid-1990s."

Until vaccines become available, many doctors urge that a combination of condoms and spermicides be used to prevent sexual transmission of AIDS. Laboratory tests show that nonoxynol-9, the active ingredient in many U.S. spermicides, can prevent the virus from reproducing. A more potent product, under development by Exovir in Great Neck, N.Y., would contain both nonoxynol- 9 and alpha interferon, a combination that compounds the killing effect. Pharmatex, a spermicide sold in Europe and Africa, also appears to inhibit the virus in the test tube.

Still, in the immediate future, education, not medicine, may well be the single most important weapon in stemming the spread of AIDS. Educational campaigns directed at homosexuals, urging them to limit their number of sex partners and adopt "safe sex" practices, have already paid off. A study conducted at the University of California, Berkeley has shown, for example, that the rate of new AIDS infections among gay men in San Francisco fell from an 18% increase each year between 1982 and 1984 to only about 4% in 1985.

U.S. Surgeon General C. Everett Koop wants to take the message to the general public and even into junior high school classrooms. Though his proposal for early education has met with resistance from religious and conservative groups, Koop is insistent. While pushing his program before a gathering of religious broadcasters in Washington, D.C., last week, he declared, "This is not an age for the faint of heart or of soul."

Most health officials believe the Federal Government will have to take a larger role not only in education but in other areas if an AIDS disaster is to be avoided. More drug-treatment centers, and perhaps even programs to give addicts free sterile needles, may be needed to control the rampant spread of AIDS among intravenous drug users. A free needle program has been highly successful in Amsterdam, known as Europe's drug capital.

Government may have to step in where underwriters fear to tread. Of 325 insurance companies surveyed in 1985, 91% refused to issue policies to people who come up positive on the AIDS blood tests. (Many insurance companies are now requiring high-risk applicants to take these tests.) Without insurance, few Americans can handle the estimated $60,000 to $75,000 lifetime cost of treatment for AIDS, and most AIDS patients are not immediately eligible for Medicare or Medicaid. To fill the gap, Senator Ted Kennedy and others in Congress have proposed that all states establish a pool to provide insurance to people who would otherwise not be covered. Nine states already have such programs.

Last week CDC officials announced plans for a public forum to discuss further steps aimed at controlling the epidemic. At issue: whether AIDS blood tests should be made mandatory for couples seeking a marriage license, for women receiving prenatal care, and for people being admitted to hospitals and clinics where sexually transmitted diseases are treated. A premarital test, says Dr. Walter Dowdle, a deputy director of the CDC, "could provide an opportunity for counseling and protect the noninfected potential partner as well as future children."

Slowly, as it touches more and more aspects of everyday life -- the education of children, marriage rites, sexual habits, health care and insurance -- AIDS will transform American society. "By 1991," says Michael Gottlieb, the physician at the University of California, Los Angeles who identified some of the first cases of the disease, "most people in certain cities will know someone who has died of AIDS." Indeed, the CDC announced last week that in 1985, AIDS jumped from 13th to eleventh place as a cause of premature mortality in the U.S. Adults now in their 40s and older remember growing up with paralytic polio -- avoiding swimming pools and crowds during epidemics, being subject to quarantines in summer camps. Today's children, says the CDC's Curran, will have other memories. "They are growing up in a society with AIDS."

CHART: TEXT NOT AVAILABLE

Credit: TIME Chart by Joe Lertola.

Caption: THE GROWING MENACE Cumulative number of U.S. AIDS victims in thousands.

DESCRIPTION: Lines indicating number of AIDS victims in total and heterosexual populations on scale of 0 to 260 for the years 1981 to 1991, with figures of man, woman and ghost.

With reporting by Dick Thompson/Washington, with other bureaus