Newsweek / April 18, 1983
MEDICINE

The AIDS Epidemic
The Search for a Cure

A new and deadly disease is coursing through the
country, wasting the bodies of victims, incubating in
an untold number of others who have yet to show
symptoms and triggering one of the most intensive
investigations of an epidemic in medical history.

Since it came into public view in 1981, derisively called "The Gay Plague," AIDS (Acquired Immune Deficiency Syndrome), which ravages the body's immune system, has stricken 1,300 Americans - more than half of them in the last year. And there is no cure in sight. "In my professional career, I have never encountered a more frustrating and depressing situation," says Dr. Peter Mansell of Houston's M.D. Anderson Hospital and Tumor Institute. "People who you know are likely to die ask what they can do to help themselves, and you are forced to say, more or less, 'I have no idea'."

The death toll to date - 489 - is far higher than the combined fatalities from Legionnaire's disease and toxic shock syndrome. Fewer than 14 percent of AIDS victims have survived more than three years after being diagnosed, and no victim has recovered fully. The lethal disease, first reported in the homosexual communities of New York, Los Angeles and San Francisco, has spread to 35 states and 16 foreign countries, including France, Germany and Denmark. And although gay men still account for 72 percent of cases, AIDS seems to be moving into the population at large. First, intravenous drug users of both sexes, then Haitian immigrants, and more recently the sex partners and children of both groups have been afflicted. Hemophiliacs and at least one recipient of a routine blood transfusion have also been stricken. And then there are those who fall into no apparent category.

"As the months go by, we see more and more groups," says Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases. "AIDS is creeping out of well-defined epidemiological confines." According to Dr. Jeffrey Koplan, a public-health expert at the U. S. Centers for Disease Control in Atlanta, Ga., AIDS will begin appearing with greater frequency among heterosexuals as the epidemic grows. And growth is one thing most AIDS researchers seem sure of: by the end of this year, predicts Dr. James Curran, head of CDC's AIDS Task Force, there will be more than 2,000 cases. "It has caught everybody by surprise," says Dr. Abe Macher of the National Institutes of Health. "Textbooks are being rewritten. We're observing the evolution of a new disease."

The first cases of AIDS apparently sprang up almost simultaneously in New York, San Francisco and Los Angeles. In January 1981 a 31-year-old male model arrived at the emergency room of UCLA Medical Center with a severe fungal infection in his throat that almost completely blocked his esophagus. The patient, a homosexual, had also suffered a drastic weight loss in the previous months and weighed barely 100 pounds. Immunologist Dr. Michael S. Gottlieb was puzzled. The unchecked growth of the white, curdlike fungus suggested a breakdown of the man's natural defenses, but he didn't fit any classic descriptions of immune disorder. Two weeks later the patient developed a devastating lung inflammation. The diagnosis: Pneumocystis carinii pneumonia (PCP). A rare parasitic lung infection usually accompanied by fever and increasing shortness of breath, PCP is seen almost exclusively in cancer or transplant patients taking drugs that suppress their immunity.

Spots: "We thought we'd never see someone like him again," Gottlieb recalls. But to his astonishment, within a few months he treated two more patients with PCP and "other infections they should not have had." Like the first victim, who gradually wasted away and died of multiple infections in December 1981, all the new cases were young, previously healthy homosexuals.

At about the same time, Dr. Alvin Friedman-Kien, a New York University dermatologist, examined a homosexual man suspected of having Hodgkin's disease. Other physicians had noted his enlarged spleen, swollen lymph glands, prolonged fever and weight loss, but they dismissed the unusual purple-red spots on the man's leg as bruises. Not Friedman-Kien. "It looked to me like Kaposi's sarcoma," he says, "but I'd never seen it in a young man before." Biopsies of the lesions and lymph nodes confirmed his diagnosis - and two weeks later the dermatologist had his second case. Inquiring among his New York colleagues, he learned that several of them had diagnosed KS in homosexual patients as far back as 1979. Aware that San Francisco also has a large gay population, Friedman-Kien called Dr. Marcus Conant, associate professor of dermatology at the University of California Medical Center there. "Two days later he called me back and reported that they had two KS cases," says Friedman-Kien. "He asked me, 'How the hell did you know we'd have them?'"
[See Graphic 1]
Rare: Something unusual and frightening was happening. In the United States, Kaposi's had always been a rare and mild skin cancer, ordinarily found in much older men of Mediterranean ancestry. But in these young homosexuals, the cancer was aggressive and quite lethal. The distinctive dark purple lesions were invasive and fast spreading, often attacking internal organs. This normally indolent disease, it appeared, had developed a fierce new personality.

In the summer of 1981, Gottlieb and Friedman-Kien reported their findings in the CDC's Morbidity and Mortality Weekly Report. Whether the patients had KS, PCP or both, the investigators noted, they all showed an unexplained depression of their immune function. The articles, published a month apart, kicked off the medical detective work at the CDC, which was so far assigned more than 100 medical sleuths to the AIDS mystery. Because the early cases were all homosexual men, the agency immediately launched a study comparing the patients with healthy gays looking for clues in the victims' life-styles or medical histories that might explain their vulnerability to the puzzling syndrome.

Partners: The investigators discovered several differences in the two groups. The gays who got AIDS, it turned out, had often had many more sexual contacts (a lifetime average of 1,100 partners) than the controls (500 partners). Not surprisingly, they had also played host to more frequent bouts of infections, including common venereal diseases like syphilis, gonorrhea and herpes, as well as the cluster of viral, bacterial and parasitic disorders that make up what is known as the "gay bowel syndrome." In addition, many AIDS patients had used amyl nitrites, the sexually stimulating inhalants called "poppers" that have been shown to produce immunosuppression.

Several theories about the cause of AIDS grew out of this first survey of gay men, only to be rejected later as the disease spread to other groups. One linked the problem to amyl nitrite. Another suggested that large amounts of sperm - also a suspected agent of immunosuppression - might cause the problem if it were absorbed by the body during frequent oral or anal intercourse. Neither of these leads held up when gays who didn't use poppers and people with less active sex lives were also identified as AIDS victims. Perhaps the most intriguing theory was "immune overload" - the possibility that repeated exposure to disease might put such a strain on the immune system that it would simply collapse, like an overburdened sea wall, leaving the body vulnerable to a flood of "opportunistic" infections like PCP or viruses that could be responsible for KS. But that idea just didn't make sense physiologically, says CDC's Koplan; the immune system doesn't wear out or crumble under pressure, and besides, there were a number of AIDS victims who had no history of multiple infections. The researchers pushed on, and although they don't yet know what causes AIDS, they are able to describe in remarkable detail what happens to its victims. A major manifestation of the disorder seems to be a malfunction of the immune system's T-Iymphocytes, a class of white blood cells that fight parasites, certain viruses, fungi and TB-type organisms. AIDS sufferers not only have too few T-cells altogether, the ones they do have are often impaired and misshapen. Typically, patients also show a reduction in the normal number of "helper" T-cells that activates the immune system. This creates an abnormally high proportion of "suppressor" T-cells whose function is to keep the system from overreacting. In healthy individuals, the ratio of helpers to suppressors is 2 to 1. Variations in this balance may occur in a number of medical conditions, but AIDS patients show persistent reversals that may be as askew as 1 to 2.

The first noticeable symptoms of AIDS, however, are not necessarily dramatic or distinctive. In fact, the syndrome can be difficult to diagnose because its early manifestations often mimic those of less serious illnesses: persistent fatigue, fever, diarrhea, night sweats and swollen lymph glands in the neck, armpits and groin, as well as a string of recurring virus infections such as colds, flu, herpes simplex and shingles.

According to the CDC, thousands of gays and others at risk for AIDS exhibit the early signs of the disease - particularly the persistent swollen glands - and it simply isn't clear whether all will develop more serious symptoms. "Maybe not everyone gets this progressive form of the illness," says CDC's Koplan. "Maybe some people get better. We don't know."

The patients who don't get better typically succumb to one or more infections that rarely hit people with intact immune defenses. Kaposi's sarcoma strikes in about a third of all cases; others get the deadly PCP (average survival after diagnosis: seven months) and a virulent form of herpes that attacks the central nervous system, as well as toxoplasmosis, a parasitic infection that can cause serious brain damage. But how victims contract AIDS in the first place remains a crucial question, and a possible model has been found in a much more common disease: hepatitis B. This debilitating liver disorder, caused by a virus, strikes the same groups as AIDS: homosexuals, Haitians, intravenous drug users, hemophiliacs and recipients of blood transfusions. It is known to be carried in body fluids, including blood, semen, saliva,
sweat and mucus. Could AIDS also be a virus, transmitted in the same manner?

Liaisons: Among gays, sexual transmission of AIDS is almost a certainty. Through exhaustive case tracking, CDC researchers were able to trace sexual encounters between 40 patients in 10 different cities-no small accomplishment, considering how many liaisons among gay men take place in the anonymity of the bathhouses. But mapping these sexual histories revealed an ominous pattern: the incubation period for AIDS (the time between infection and the onset of symptoms) varies from a few months to more than two years. If, like many diseases, AIDS turns out to be contagious during this "latent" stage, next year's victims - who may be feeling perfectly healthy today - could unknowingly be infecting hundreds or even thousands of others.

Intravenous drug users make up the second largest category of AIDS victims, with more than 16 percent of the total cases. Not all are addicts, explains Dr. Gerald H. Friedland, who has treated more than 50 of these patients at Montefiore Hospital in the Bronx, N. Y. Some use the drugs recreationally, he explains, "but they probably all shared needles." According to one young AIDS sufferer who used to shoot heroin and cocaine twice a week, the same needle might "hang around for three or four weeks" in one of the "shooting galleries" where addicts congregate. "You take a needle from someone else," he explains, "rinse it off to make sure there's no blood, use it and pass it on to the next guy - like a reefer." Obviously, the perfunctory rinsing of the needle offers little protection. Some researchers suspect that the reason AIDS has spread to this group may be that 5 percent of the homosexual victims also shoot drugs.
[See Graphic 2]
Drawback: Arguably, drug users are taking a known health risk when they shoot up - especially with dirty needles - but most of the nation's 20,000 hemophiliacs have no choice about exposing themselves to possibly contaminated blood on a regular basis. During the past decade, the lives of many hemophiliacs have been revolutionized by the development of a freeze-dried clotting agent called Factor VIII concentrate, which can be mixed with water and injected in just a few minutes to stop a bleeding episode. (An older version of the clotting factor, cryoprecipitate, is much less convenient to store and administer.) But Factor VIII concentrate has one serious drawback: each dose is made from the pooled plasma of up to 20,000 donors (compared with only about 40 for cryoprecipitate), vastly increasing the risk of exposure to blood-borne disease. So far, 11 hemophiliacs who used Factor VIII concentrate have become AIDS victims; eight of them have died from the illness and six other suspicious cases are being studied.

If hemophiliacs can catch AIDS through donated blood, what about the risk to the 3 million other Americans who require blood transfusions every year? "The evidence for a contaminated national blood supply is very weak," observes Yale University's Dr. Joseph Bove, chairman of the American Association of Blood Banks' committee on transfusion-transmitted diseases. So far, only two post-transfusion patients have gotten AIDS, and only one - a San Francisco infant who suffered from Rh incompatibility - has been subsequently linked to an infected donor.

Nonetheless, several other cases of AIDS-like illnesses in post-transfusion patients are under investigation, and the U.S. Public Health Service last month asked physicians to encourage patients who might need transfusions during surgery to donate their own blood for that purpose ahead of time. The government also recommended that all blood and plasma collection centers advise donors in high-risk groups to refrain voluntarily from giving blood. At least one large plasma manufacturer in Los Angeles rejected nearly 400 homosexual donors in one month. To avoid stigmatizing potential donors in high-risk groups - particularly gay men - blood-collection agencies usually don't ask outright about their sexual orientation. The New York Blood Center, for example, gives donors a written description of AIDS symptoms and a list of the high-risk groups. In privacy, the donor can then check either of two instructions: "My blood donation may be used for transfusion" or "My blood donation should only be used for studies."

Some of the most tragic victims of the epidemic are approximately 20 children - all under the age of four-who have developed immune deficiencies that look very much like AIDS to the CDC. Nearly all of the children were born into households that included relatives at high risk for the disease. Dr. James Oleske, an immunologist and specialist in infectious diseases at the New Jersey Medical School in Newark, has treated II such children, 4 of whom have died, 3 of PCP. Some researchers have questioned whether the youngsters may have had a more common form of congenital immune deficiency instead of AIDS, but Oleske insists that it's not very hard to tell the difference. For one thing, the children he has treated have higher antibody levels and less stable immune systems than children with more conventional inherited immunity problems have. Moreover, only one child in a set of identical twins Oleske diagnosed had the AIDS-like disorder, weakening the case for a genetic explanation.

Twist: If the cases among children are the most wrenching, what has come to be known as the "Haitian connection" is the most baffling twist in the AIDS mystery. At least 35 immigrants from the Caribbean island, most of whom settled in Miami and New York, have come down with the disease. In addition, more than 50 cases of AIDS have been reported in Haiti.

Because the Haitian victims are neither hemophiliacs nor - apparently - homosexuals or intravenous drug users, they offer scientists an important opportunity to study how the disease might be transmitted other than through blood or sexual contact. (One Miami researcher has suggested that the water supply in Haiti should be scrutinized for a possible contaminant.) Dr. Jean-Claude Desgranges, a Haitian physician serving a fellowship at Long Island Jewish Hospital, heads a committee that is investigating AIDS in the New York Haitian community. The study will include thorough immunological evaluations of healthy Haitians, as well as an examination of their life-styles, to determine what might predispose them to the illness. "We don't know absolutely whether some of the AIDS patients are in fact homosexual or drug addicts," warns Desgranges. "They might not admit it because those things are taboo in our society."

Haiti is a popular holiday spot for American homosexuals, and a persistent theory holds that vacationing gays either brought the disease home with them -- 0r took it there in the first place. But according to Dr. George Hensley of Jackson Memorial Hospital in Miami, the cases on the island were diagnosed at almost exactly the same time as the first patients in the United States, clouding the mystery still further. "My suspicion is that the place of origin is unknowable," says Dr. Sheldon Landesman, who has treated more than 20 Haitians at Downstate Medical Center in Brooklyn.

Samples: Although scientists may never know with certainty the precise geographical birthplace of the AIDS organism, researchers at CDC are determined to gather every scrap of information they can glean about this alarming new arrival on the medical landscape. Dozens of specimens of blood, body fluids and biopsied tissue arrive weekly at the complex of government laboratories in Atlanta. Some of the samples are placed in cell cultures; others are injected into mice, cats, dogs and chimpanzees. But so far, the elusive AIDS organism has failed to grow in the petri dish - and none of the lab animals has developed a single symptom of the disease.

By coincidence, AIDS investigators may have found a useful animal model for the disease in a place they didn't even look. At the University of California Primate Research Center in Davis, an epidemic of an immune deficiency disease with symptoms almost identical to AIDS has broken out in a colony of monkeys. Twenty-seven animals in one cage of 77 rhesus monkeys developed swollen glands, diarrhea, fever, weight loss and a rare form of skin cancer - very much like the human AIDS patients. All the sick monkeys died within 18 months, many from severe infections. A similar disorder has killed 60 monkeys at Harvard's New England Regional Primate Research Center.

Roy Henrickson, senior veterinarian at the Davis facility, hopes to be able to create a laboratory model of the animal disorder that might shed some light on the cause, transmission and possible treatment of AIDS. Although the monkeys' malady is not identical to AIDS, NIH veterinarian William Gay points out that the riddle of polio was solved largely through research on a disease in monkeys that also wasn't quite the same as the human illness.

So far, the Jonas Salk of AIDS has not emerged. There are still no experts, laments Dr. Joel Weisman, a Los Angeles physician who has treated many gays with AIDS. "The expert will be the person who finds the cause and the cure. But for now, there is no penicillin, no polio vaccine for AIDS." Despite the frustrating nature of the disease, AIDS has aroused enormous interest among researchers. "It's a fascinating problem," says Dr. Robert Biggar of the National Cancer Institute. "We get excited about it until we remember it is killing people.

The scientists are also troubled by what many consider inadequate funding for AIDS research. Everybody is operating under enormous budget constraints," says Friedland. "To stem the tide we've had to beg, borrow and steal people away from other projects." NIH will grant $7.9 million for AIDS research in fiscal 1983, more than twice as much as last year. But nobody can state exactly how much is being spent on the epidemic, explains Dr. Robert Gordon, who is coordinating AIDS-related research at NIH, because so many long-term grants for basic research, in fields like immunology, involve work that is applicable to AIDS. Nonetheless, U.S. Rep. Henry Waxman has introduced legislation allocating an additional $40 million for research into diseases like AIDS that qualify as public-health emergencies. But even a funding windfall won't provide quick answers to the basic questions AIDS raises. For example, scientists don't even agree on exactly what it is they're looking for. While Curran and others are convinced the disease is caused by a brand-new organism, several researchers believe the agent may be a familiar pathogen such as cytomegalovirus (CMV) - commonly found in most of the high-risk groups - that has recently mutated into a particularly lethal form. Host factors, such as genetic susceptibility, says Gottlieb, could determine why people get such different manifestations and degrees of the disease.

Jungle: Other researchers suspect that AIDS may have existed for years in a tropical region like Haiti or Africa and only recently migrated to the United States and Europe. In extremely underdeveloped areas, where medical monitoring is comparatively primitive and lack of modern sanitation makes severe infections commonplace, a full-scale AIDS epidemic could conceivably go undiagnosed, lost in a jungle of other life-threatening illnesses. In fact, a virulent strain of KS has long been prevalent across a band of quatorial Africa that also has a high incidence of cytomegalovirus infection; and in the United States, CMV has been cultured from KS lesions.

The "African genesis" theory is espoused by a French immunologist, Dr. David Klatzmann, who reports that among France's 40 AIDS victims, several who were heterosexual had lived or traveled in western Equatorial Africa. Yet another link to Africa is postulated by Dr. Caroline MacLeod, director of the University of Miami's Tropical Diseases Laboratory. She suggests that Cuban soldiers returning from military duty in Angola might have brought AIDS home with them, and that eventually the disease might have spread to the Cuban community in Miami.

Researchers are also trying to track the path of the disease from its very earliest stages within various specific populations. NCI's Biggar is studying the spread of AIDS among homosexuals in Denmark, where seven cases have been confirmed so far, but many more gays in a large group who were screened showed significant T-cell abnormalities. "It's like looking at the picture in the United States in 1980," says Biggar. At New York's Mount Sinai Hospital, Dr. Irving J. Selikoff is gearing up a prospective three-year study of 1,500 people who are in the various high-risk groups but have not developed any symptoms of AIDS. He hopes that the project will be able to identify early - appearing abnormalitiesthat might allow doctors to derail the relentless progress of the illness. "Treatment of AIDS is so unsatisfactory," he says, "if we don't prevent it, we're in serious trouble."

Indeed, treatment of AIDS patients has been remarkably unrewarding. Although drugs can sometimes cure the opportunistic infections, the patients' severely weakened immunity leaves them vulnerable to one illness after another. Physicians at New York's Memorial Sloan-Kettering Cancer Center and several other institutions are giving AIDS sufferers varying doses of interferon, a natural virus-fighting substance that has shown promise in treating certain types of cancer. Secreted in minute amounts by cells throughout the body, interferon is believed to interfere with virus replication and to slow cell division in tumors. While some patients with Kaposi's have experienced significant remissions with interferon therapy, none has recovered normal immune function. And, cautions Gottlieb, "we don't know how many of these people will be alive in five years." Other KS patients have responded to conventional anticancer chemotherapy, but critics wonder whether such drugs might actually worsen AIDS by increasing the suppression of the immune function.
[See graphic 3]
Physicians have tried other approaches, including bone-marrow. transplants, replacement of blood plasma with plasma from healthy donors and experimental extracts of T-cells called transfer factor. So far, patients have failed to respond dramatically to any of these therapies. Dr. Spartaco Bellomo of St. Michael's Medical Center in Newark, N.l., sums up the frustration of many practitioners when he observes that trying to treat AIDS patients is like "throwing darts at a dartboard - blindfolded."

The anguish wrought by AIDS is not confined to those already afflicted and the despairing doctors who cannot cure them. The specter of a killer disease, inexorably mowing down its young victims, has ignited the fears of thousands of ordinary Americans. Where will AIDS strike next, they wonder, and could they become victims? Fortunately, the prognosis for most people is reassuring. "We are not dealing with the Black Plague," declares Dr. Ilya Spigland, chief of virology at Montefiore. "You're not going to get AIDS from toilet seats or eating in restaurants." Ninety-five percent of AIDS victims have identifiable risk factors; the disease doesn't strike at random, and does not seem to be spread by airborne droplets of a cough or sneeze, like influenza. Most physicians agree that extremely intimate contact - or exposure to blood - is probably necessary for infection.

The hundreds of doctors, nurses, lab technicians and scientists who, during the past four years, have cared for AIDS patients, drawn their blood and worked closely with specimens of their body fluids, are understandably worried about their own vulnerability to the disease. Because hepatitis B is a common occupational hazard for this group, they seem like logical targets for AIDS as well. So far, not a single case of AIDS has been reported among health workers. Nonetheless, they have been warned by the CDC to "avoid direct contact of skin and mucous membranes with blood, blood products, excretions, secretions and tissues of persons judged likely to have AIDS."

Advising patients who already have AIDS is a far more subtle matter, often requiring a delicate touch. "It's very hard to tell a young, not desperately ill person that he should not have sex at all for the rest of his life," explains Montefiore's Friedland; instead, he urges his patients not to acquire new partners and to use condoms. He also suggests that they not share towels or prepare food for others. "But in reality we don't know precisely what to tell people," Friedland admits. "We don't know the period of communicability; you may be dying of AIDS and no longer contagious."

Fire: "We don't know" remains the frustrating answer to almost all questions about AIDS. We don't know what causes the disease, we don't know how to treat it and we don't know whether the epidemic is about to level off or race through the population like a forest fire. For the moment, reports CDC's Curran, with three to five new cases reported every day, "there are no signs of any slowdown." But most researchers believe that outside of the homosexual community, the AIDS curve will rise much more slowly. And while a full understanding of what causes the disease may be several years away, a breakthrough leading to a successful treatment could come much sooner. Until it does, says Dr. Frederick Siegal of New York's Mount Sinai Medical Center, the intensive search promises to unlock some of medicine's deepest secrets about how the body protects itself - or fails to-against infection and cancer. But, he admits, "it's a very small silver lining to a very big, very dark cloud."

JEAN SELIGMANN with MARIANA GOSNELL
in New York, VINCENT COPPOLA in Atlanta,
MARY HAGER in Washington and bureau reports

Newsweek / April 18, 1983