A mystery in the blood

For 18 months, medical investigators tracked the lethal epidemic as it surfaced in one subculture after another.

First it turned up among homosexuals in New York and California. Then among Haitian immigrants. Then intravenous drug users, and then hemophiliacs.

Epidemiologists feared it would soon strike the general population, an alarming possibility since the disease had already led to the deaths of nearly 40 percent of all its victims and no one knew its cause or cure.

A particularly sinister disease, it attacks the victim's immunity system, leaving the patient vulnerable to viruses, funguses and cancer. Although doctors can effectively treat most of these infections, even the cancer, the underlying immune deficiency persists until, finally, one infection defies treatment. And the patient dies.

The disease is called AIDS (acquired immune deficiency syndrome). For a while it looked as though AIDS would stay confined to a few high-risk populations, but last month the Centers for Disease Control in Atlanta announced that a California baby had developed AIDS -like symptoms after a blood transfusion.

CDC doctors are not sure why the child became ill, but one of the blood donors was a San Francisco man who subsequently developed AIDS and died.

Largely because of this, and because a rising number of hemophiliacs are developing AIDS , the federal government has hastily called a meeting to discuss what to do. On Tuesday, 30 blood specialists from all over the country - along with representatives of the gay community - will converge on Atlanta.

The concern is that the nation's supply of blood for transfusions might become contaminated with whatever it is that causes AIDS.

AIDS is still quite rare. Yet it has provoked the most intense, sustained epidemiologic search in history. Never before has the CDC concentrated so many researchers for so long on a single epidemic. Despite this massive effort, researchers remain almost totally baffled as to what causes AIDS or how it is spread.

Yet AIDS has sparked even more hope than fear. Cancer researchers consider it one of the most interesting leads in years. Many doctors think that AIDS may help them better understand how the immunity system works, and how it can be used to ward off not just AIDS but a host of other illnesses, even cancer.

One researcher, Dr. Roger Enlow of the Hospital for Joint Diseases in New York City, has compared the research opportunities made possible by AIDS to the breakthroughs that led to the development of penicillin.

Never before has science confronted an epidemic in which the primary disease only lowers the victim's immunity and then it is a second, unrelated, disease that produces the symptoms and does the killing.

The two diseases that most often kill AIDS victims are Kaposi's sarcoma, a rare form of skin cancer, and Pneumocystis carinii pneumonia, a rare form of lung disease.

Since AIDS seems to precede development of Kaposi's, the epidemic provides strong evidence that this cancer, and possibly other cancers, infect people only when their resistance is low. Better understanding of the immune processes might lead to new ways of strengthening the body's natural ability to fight off disease.

Already, scores of laboratories here and abroad are exploring such questions.

Some researchers are giving AIDS patients the promising new drug interferon to see whether they can wipe out Kaposi's by raising the patient's immunity rather than attacking the tumors directly with drugs.

Other researchers are investigating the disturbing possibility that repeated severe infections, such as are common among intravenous drug users and sexually active gays, might permanently exhaust the immune system, dooming patients to eventual fatal infections.

Much more deadly than Legionnaires' disease or toxic shock syndrome, the AIDS epidemic has struck more than 800 people in this country and 66 persons in 13 foreign countries in the last two years. More than 300 of these people already have died, and some researchers think that eventually disease will kill 70 to 80 percent of the people with AIDS.

Although AIDS is still a rare disease, the number of known cases has been doubling every six months. Almost 600 of the cases were diagnosed last year.

At first, only homosexuals were stricken, but the epidemic started spreading into the straight community last year, so that now 25 percent of all victims are heterosexuals. The CDC expects the percentage to keep rising.

The epidemic also has had a profound sociological impact. It has traumatized the gay communities in New York City, where nearly half the world's known AIDS cases have been reported; San Francisco, and Los Angeles.

Because sexually active and promiscuous gays are much more likely to get AIDS , many gays have drastically altered their lifestyles, avoiding pickup bars, bathhouses and other places where group sex occurs.

Finding themselves under attack by some public health authorities, who blame a promiscuous gay lifestyle for the disease's rapid spread, the traditionally unorganized New York City gays have, for the first time, united in a common goal to protect their community.

New York gays have formed an impressive self-help group called the Gay Men's Health Crisis (GMHC), which already has attracted more than 300 volunteers.

Not only does GMHC put out the most authoritative periodic review of doctors, services and developments in AIDS research, but it also has raised more than $100,000. The money will fund research, provide psychotherapy groups for emotionally traumatized victims and establish a home-care service for gay victims without friends or family to care for them. GMHC has even bought out the 17,000-seat Madison Square Garden for the Ringling Bros. and Barnum & Bailey Circus for a night in April to hold the biggest gay event in history: a fund-raiser to fight AIDS.

The events leading up to Tuesday's emergency meeting in Atlanta began more than three years ago in New York City. Young men, some of them in top physical shape, started coming down with diseases that usually afflict only the weak or the elderly.

The first of these cases was seen at the New York University Medical Center, which is just a short cab ride from Greenwich Village and is very popular with the large homosexual population living there.

The early symptoms did not seem particularly threatening. The patients developed lymphadenopathy - lymph glands in the neck, groin or underarms became swollen and stayed that way for months - and they felt very tired. Some began to lose weight rapidly. Some had muscle aches, sore throat, slight fever, cough, shortness of breath. It was an ailment easily confused with a cold or some other minor problem, except that the symptoms persisted.

But it was not so easy to dismiss the lesions - small purple spots - that began appearing on the torso, legs or face. So these gay men, who had not felt well for months, made the trip to NYU, where they were told they had Kaposi's sarcoma.

The NYU doctors were baffled to see this disease in such young people. Kaposi's had never struck young, otherwise healthy people, presumably because, unlike the elderly or debilitated, their immunologic systems were vigorous enough to fight off whatever it was that caused this type of cancer.

Kaposi's victims usually were people over 60 or kidney transplant patients whose immunologic systems had been purposely depressed to prevent rejection of the transplanted organ.

But the NYU patients were mostly in their 30s, and their type of Kaposi's was much more deadly than usual. Half of NYU's young patients were dead within 20 months, whereas elderly patients with Kaposi's usually survive for eight to 13 years.

There was only one clue to a cause: All the victims were homosexual and all had been infected with cytomegalovirus (CMV), a ubiquitous herpes virus that usually causes no symptoms.

A few months after the young men started turning up at NYU with Kaposi's in 1980-81, doctors in Los Angeles and San Francisco started seeing young men with Pneumocystis carinii pneumonia (PCP). Pneumocystis was a completely different disease from Kaposi's, but there was one similarity - it usually struck only debilitated people, such as transplant patients or malnourished infants.

The backgrounds of the 10 victims in San Francisco and Los Angeles were also strikingly similar to the Kaposi's victims in New York:

They were all homosexual, and they all had been infected with CMV. Two of the five San Francisco patients had Kaposi's as well as Pneumocystis.

Word of the three strange outbreaks was routinely passed on to the Centers for Disease Control, the federal agency that keeps track of epidemics and tries to find their causes before they spread out of control.

The CDC is to public health what the FBI is to the justice system, a crack corps of disease detectives, mostly eager young men and women recently out of medical school, who might spend months or years tracking diseases throughout the world.

It was the CDC that solved the mystery of Legionnaires' disease in 1977, and it was also the CDC, in 1980, that discovered the association between tampons and toxic shock syndrome. Now, in early 1981, the CDC was confronted with an even more baffling disease, one that would eventually claim more lives than both of these other epidemics combined.

Realizing the frightening threat of the new epidemic, because it was highly lethal and its cause was unknown, the CDC immediately gave it high priority and named Dr. James W. Curran to head a 10-member task force. This task force eventually would grow to more than 100 people.

Curran, 37, clean-shaven and always neatly dressed in a tie and jacket, is known to his colleagues at the CDC as a meticulous and hard-working investigator.

Curran and his team started poring over the case histories of the patients in New York and California, looking for some common thread that might explain why they should fall victim to such different types of disease.

Concerned that they were seeing only the tip of an epidemiologic iceberg, the CDC surveyed physicians in 18 major metropolitan areas by letter and by telephone, to see whether they had been seeing young people with Kaposi's, a distinctive disease that was easy for physicians to spot. They also contacted the heads of infectious disease, dermatology, cancer and pathology departments in all major hospitals in those communities.

Eventually the epidemiologists would discover AIDS in most major cities, including Philadelphia, where eight cases have been found. But these initial surveys indicated that the epidemic was largely confined to New York, San Francisco and Los Angeles.

Immediately apparent to the investigators was the fact that all known victims were gay and all had been exposed to the cytomegalovirus. But 8 percent of the male population was believed to be homosexual, and cytomegalovirus was common among gays. Why did these homosexuals get sick and not others?

Using one of the most common tools of the epidemiologist, Curran organized a case-control study, in which he compared the AIDS patients with a control group - that is, a group of people similar to the AIDS patients in all respects except that they were healthy. The control subjects in this study were all gay, the same age, from the same parts of the gay communities and from comparable ethnic backgrounds.

The plan was to match them in all known respects and then look for some difference between the two groups. Hopefully, that difference would be what caused the disease.

Differences did emerge. The AIDS patients had had sex with many more people than the healthy gays, and they used more "poppers," amyl or butyl nitrate, a drug that enhances the sexual experience by dilating the blood vessels and relaxing the sphincter muscles for anal sex.

Even though the control subjects were taken from venereal disease clinics, and hence were probably more sexually active than most, the control subjects averaged only 25 sexual partners each per year, compared with 60 per year for the AIDS victims.

This suggested that AIDS was a sexually transmitted disease, but there was no evidence of person-to-person spread. None of the victims had had sex with anyone who had AIDS , or at least they did not think so.

Dr. David M. Auerbach, the CDC officer assigned to Los Angeles, started interviewing the California AIDS victims, mainly in an effort to find out how the disease was spread.

In a long questionnaire, Auerbach asked people about the drugs they used, the places they went for recreation, the diseases they had had recently. Many questions centered on sexual practices. He asked the sex of their sexual partners, how often they had sex, and with how many different people. He interviewed friends and lovers of the victims. And, he reviewed medical records to see whether there might be some symptom or sign that suggested the person was going to get sick.

Working with local health officials, he obtained specimens of tissue, semen, feces, blood and other body fluids, which were flown back to the CDC in Atlanta for laboratory analysis.

Auerbach's counterparts in New York, and later in other cities across the country, did the same thing, and the samples and information began to grow.

Soon it was clear that the AIDS victims had long histories of medical problems. Nearly all of them had been infected with the cytomegalovirus and many with the Epstein-Barr virus (EBV), which causes mononucleosis and is associated with Burkitt's lymphoma, a type of cancer rarely found in this country but common in some parts of Africa. Hepatitis was also common among this population, as were gonorrhea, the parasitic infection amebiasis and lymphadenopathy.

Lymphadenopathy is a common response by the body to disease, but the glands return to normal size after the infection is gone. Rarely are they swollen for more than several weeks. The AIDS patients had had lymphadenopathy for several months.

All this information was interesting and would be valuable in guiding the lab people in their search for the disease-causing agent, but the big question was still unanswered:

How was the disease spread?

Homosexuals in California started hearing rumors that a strange epidemic was going through the gay community, and Auerbach was mentioned as the person to contact whether anyone had information that could help solve the mystery. Auerbach started getting phone calls.

One man called and said two of his acquaintances had come down with AIDS and that they had had sex with each other. Was it possible, the caller wondered, that you could get this disease like gonorrhea or other venereal diseases? Others called with similar information, and Auerbach started following the leads to see whether there was a sexual link among cases.

Working with a list of 19 men who had developed Pneumocystis or Kaposi's - the number of victims was climbing daily - Auerbach and physicians from local medical centers extensively questioned the patients, or, in cases of deceased victims, their friends and lovers, to develop what amounted to sexual family trees. The results were surprising.

Nine of the 19 patients had had sexual contact with other Kaposi's or Pneumocystis victims. Four of the nine had been exposed to more than one patient who had Kaposi's or Pneumocystis. Three of the patients had developed Kaposi's after having sex with people who had Kaposi's.

While this was not definitive proof of sexual transmission of AIDS, it was strongly suggestive.

One of the more ominous discoveries was that it took a long time for the first symptoms of disease to develop after sexual contact with an infected lover - from nine to 22 months.

Such a long latency period meant that undoubtedly many men, who at the moment felt in perfectly good health, were already infected with AIDS. In a few weeks or months they would be hit with symptoms - swollen glands, weight loss, congested lungs or skin lesions - and discover that they were seriously ill.

Hundreds of laboratory specimens were arriving at the CDC's laboratories in Atlanta, sent in by dozens of epidemiologists assigned to the AIDS task force.

Much of the laboratory work would concentrate on the search for viruses, which were thought to be the most likely cause of the epidemic, although other possibilities were also checked out.

The specimens for viral study went to Room 210 of Building 7. It was a large room with a hooded examining table to protect lab personnel from contamination, a refrigerator for samples and a long lab table. As soon as the samples arrived, identification codes for each specimen were entered by hand in a bound record book. If a virus was found, the researchers could check back by number and determine from where it had come.

Half the samples were frozen, so they could be examined later, if and when the disease-causing agent was found. The other samples, kept in screw-top test tubes, went from Room 210 to dozens of different labs scattered about the complex of CDC buildings.

Tiny bits of biopsied tissue, taken from the lungs of Pneumocystis patients and the lesions of Kaposi's victims, went to the electron microscopy room, where microscopists searched for visual evidence of the pathogen, or disease- causing agent.

Other samples of white cells and bodily fluids went to laboratories where scientists attempted to grow the bug out of hiding. Here the AIDS' specimens were inoculated onto sheets of embryonic and lung cells growing in laboratory dishes. If viruses were present and grew out, they would make their presence known by disrupting the smooth surface of the sheet of cells with their multiplying numbers.

Other white cells were taken next door to the animal building, where technicans injected them into the bellies of mice. The mice were kept in an isolation room with double doors and negative pressure, to prevent any disease that might start growing in the animals from contaminating the CDC's buildings. The mice would be inspected every day to see whether they lost weight, became listless or in other ways showed that they were getting sick.

Because some people thought the disease might be associated with street drugs rather than viruses, a different set of mice were injected with the ''poppers" used by many gays.

Because of the exciting research opportunities opened by this unique epidemic, CDC scientists were joined by scores of other scientists in New York City, Los Angeles and San Francisco and at the National Institutes of Health in Bethesda, Md.

Much of the work went down paths that dead-ended, but the disease detectives made one very exciting discovery - how the disease impaired the victim's immune system, preventing it from fighting off infection.

Using the new technology of monoclonal antibodies and other cell-analysis techniques, the researchers honed in on the immune deficiency with a precision not possible as recently as five years ago. This knowledge did not immediately help them in treating victims, but the disease gave scientists a remarkable perspective on the immune system in general and a chance to learn how immunologic deficiencies lead to many of the diseases that plague society.

Specifically, the laboratories found that many AIDS patients had too few of what are called T-helper lymphocytes, the cells that help turn on the body's immune response, and comparatively too many T-suppressor lymphocytes, the cells that help turn the process off. In the vernacular of the trade, their T- cell ratio was off.

It's all a terribly complicated business and, until AIDS came along, of interest only to immunologists and related scientists. But soon the homosexual community was talking about "T-cells," "ratios" and "helper" and ''suppressor" cells as easily as a flu victim talks about his temperature.

''My ratio is much better," a patient would tell a friend after receiving the latest lab results. Or, "I'm afraid my helper cells are down. "

AIDS patients saw it all as a full-scale battle being waged inside their bodies. The analogy was a fairly accurate one. The T-helper cells are comparable to artillery spotters, who identify the invading disease as it enters the body and call in a bombardment of macrophages, antibodies and other proteins the body manufactures to fight off infection. At the other end of the regulatory process are the T-suppressor cells, which call off the bombardment when it looks as though the battle has been won.

In a healthy person, it is a beautifully balanced system. But in an immunologically deficient person, such as an AIDS victim, there are too few helper cells to head off the infection, and what little response the body does make is quickly turned off by the excess number of suppressor cells.

Immunologically healthy people have twice as many helper cells as suppressors (a ratio of 2), but many AIDS patients had the opposite ratio. They had two suppressor cells for each helper, or a ratio of 0.5, or worse.

This was a particularly ominous finding, because it meant that successful treatment of the obvious infection, like Kaposi's or Pneumocystis, only bought time for these patients. Because the underlying immune deficiency persisted - doctors had no proven way of treating it - the AIDS victims were, as one doctor put it, pathologic time bombs waiting to explode.

Because AIDS initially appeared to be a disease limited to homosexuals, many physicians thought it resulted from the extreme sexual promiscuity common among some members of the gay community.

In fact, AIDS was originally called GRID (Gay Related Immune Disease), an acronymn that annoyed vocal members of the gay community, who already were feeling under attack for their lifestyle.

This acronym, however, and some of the theories had to be changed in July 1981, when the CDC found out that heterosexuals also were getting AIDS. That month, eight heterosexual cases were reported, but by then 10 times that number of gay cases had been uncovered. Straights accounted for only 8.7 percent of cases.

In the next few months, however, the number of straight cases quadrupled to 34, so that by the end of 1981 they constituted 16.5 percent of the 205 cases then listed. What was striking about these new cases was that most of them - 22 in all - involved intravenous drug users.

This tended to challenge the theory that AIDS was transmitted only through sexual contact. Since intravenous drug users were commonly vulnerable to blood-borne diseases carried on dirty needles, the assumption was that the same microorganism was causing AIDS in both groups, but that the mode of transmission was different.

The epidemic continued to spread at an alarming rate. It had more than doubled, to 439 new cases, by the middle of last year. Heterosexuals accounted for 97 cases, or 22 percent of the total. But now there was yet another confounding factor - the emergence of Haitian victims. Twenty-six of the new heterosexual cases were people who had immigrated from Haiti.

Discovery of yet another high-risk group was so disturbing that the CDC featured the outbreak in its July 9 MMWR (Morbidity and Mortality Weekly Report), but by publication time the total had climbed to 34 Haitians in five states.

Most of these victims lived in Florida, where the new Haitian arrivals landed, and in Brooklyn, where long-term residents settled. The biggest group of Haitians was seen in Jackson Memorial Hospital in Miami, where 19 patients from 22 to 43 years old were treated.

All but two of the victims were male, and all the patients had been born in Haiti and had lived in the Miami-Dade County area for periods ranging from one month to seven years. Even though AIDS was believed to have a long incubation period - a year or more - it seemed unlikely that long-time residents of the United States had brought the disease in with them from Haiti so many years earlier.

AIDS was fearfully lethal for the Haitians. Ten of the 19 had died before the MMWR could be published, and others were already very sick. They were stricken by an array of diseases, against which they were pathetically defenseless because they had severe T-cell abnormalities, including an inversion of the normal ratio of T-helper to T-suppressor cells.

Among the diseases were six cases of Pneumocystis, four cases of cryptococcal meningitis (an infection of the lining of the brain), three serious cytomegalovirus infections, widely disseminated tuberculosis, toxoplasmosis (a parasitic neurologic disease) and a serious form of herpes simplex, which in healthy people is just a fever blister.

Many patients had several of these so-called opportunistic infections at once. (The CDC called them opportunistic infections because they took advantage of the opportunity created by the victim's deficient immune system. )

Now the epidemiologists were confronted with the difficult task of coming up with a theory that could tie together such diverse groups as Haitians, gays and IV drug users. Haitian sexual practices presumably were similar to those of the rest of the population, so this was not a likely explanation, and why would Haitians be more vulnerable to blood-borne disease?

One epidemiologist postulated voodoo blood-letting rituals as a theory. Another epidemiologist discovered that Haiti was a popular vacation area for New York gays, and that male prostitution was common in Port-au-Prince, the Haitian capital. Someone else said that many years ago French slave traders had brought to Haiti slaves captured in Uganda and Kenya, parts of Africa with a high incidence of Kaposi's sarcoma and Burkitt's lymphoma.

This was probably a coincidence, but epidemiologists were particularly intrigued by the vague link to Burkitt's, because some AIDS victims had developed this rare cancer and because Burkitt's was believed to be caused by the Epstein-Barr virus, which was prevalent among gays in the United States.

The most effective drug to treat Pneumocystis, which has killed so many of the AIDS victims, is pentamidine isethionate. It is not commercially available but is distributed only by the CDC. Because Pneumocystis had been a comparatively rare disease, the CDC averaged only five to 15 requests for the drug a month.

But in the last 18 months, the requests increased dramatically, so that by the beginning of last year the CDC was averaging 60 calls a month. In this roundabout way, the CDC was able to track the spread of Pneumocystis, and hence AIDS.

Early last year Dr. Bruce L. Evatt, a hematologist and director of the CDC's division of host factors, received a call from a Miami physician asking whether any doctors were finding Pneumocystis in hemophiliac patients. Evatt said no, and asked the reason for the question. The doctor said he had a hemophiliac patient, 62 years old, who had just died of Pneumocystis.

Because the patient was already dead, it was impossible to run tests to see if the man was immunologically deficient and an AIDS victim, but Pneumocystis in hemophiliac patients had not been reported before. It could be a coincidence, but, to be safe, Evatt instructed the person handling pentamidine requests to ask physicians calling in if their patients had hemophilia.

In June, the CDC received a call from a physician in Denver, asking for pentamidine. The doctor was asked why he wanted the drug. He said he had a patient, a man, 59, with Pneumocystis and cytomegalovirus infection. Was the patient a hemophiliac? Yes he was, the doctor said.

Within hours a CDC investigator was on a plane headed for Denver. Immunologic tests were performed just before the man died. The patient had few helper cells, and the helper/suppressor ratio was reversed. It seemed likely that he was an AIDS victim.

Neither this man nor the other had been a homosexual an IV drug user or a Haitian. It looked as though AIDS was entering a new subpopulation, and the likely mode of transmission - through the blood transfusions hemophiliacs constantly receive - frightened the CDC investigators. The obvious fear was that the AIDS bug might enter the nation's blood-transfusion supply.

A third hemophiliac case was discovered a few weeks later in northeastern Ohio. The victim was a heterosexual male, 27. His helper/suppressor cell ratio was reversed.

In July, an emergency meeting of blood specialists was held in Washington. If hemophiliacs were getting AIDS , the likely mode of transmission was through transfusions of Factor VIII, a clotting component of the blood.

These transfusions were unlike the transfusions most people get in that the Factor VIII was separated from pooled blood donations coming from 1,500 to 2,000 donors. Tracking down the source of the contamination, assuming that the blood was even responsible, was virtually impossible.

The experts assembled in Washington asked what precautions could be taken. How could they guard against a disease that is caused by an unknown agent and is spread in an unknown way?

Dare anyone suggest that homosexuals, drug addicts and Haitians stop donating blood? Considering the relatively small number of people infected, compared with the many millions of people in these three subcultures, it seemed like an excessive response to what was only a possible threat. There was no proof that the disease was transmitted to the hemophiliacs through the Factor VIII transfusions.

Not only would a ban on such donors reduce the amount of blood collected, but it also would unnecessarily scare recipients of blood transfusions and would further stigmatize subcultures that were already burdened with discrimination.

It was decided to alert hemophiliac centers and specialists around the country to the possible danger and to step up surveillance of this special population, to see whether more definitive action was warranted.

The number of AIDS cases continued to climb as last year drew to a close, and the statistics were disturbing.

By mid-December, the total number of U.S. cases had reached 843, with 317 deaths. That is a mortality rate of 37.6 percent, much higher than the 20 percent mortality rate for Legionnaires' disease and higher than the rate for most of the plagues that decimated cities centuries ago.

Actually, the ultimate mortality rate probably will be much higher, because half of the cases were diagnosed during the last six months and many of those now alive probably will die soon. Kaposi's patients have an average life span of 16 months after diagnosis. The more deadly Pneumocystis kills in an average of seven months.

All the statistics show that the mortality rate increases with time. Fifty- one percent of the people diagnosed more than six months ago are dead, 68 percent of those diagnosed more than 12 months ago are dead, and of those diagnosed more than two years ago, 79 percent are dead.

Other statistics now show that:

So far, the laboratories have been unable to come up with any clues as to what causes AIDS. None of the laboratory mice have gotten sick. Researchers have now inoculated primates in the CDC's Phoenix, Ariz., animal labs, but they too remain perfectly healthy.

The epidemiologists, however, have come up with one intriguing association.

The liver infection Hepatitis B, which is caused by a virus, is prevalent in every one of the AIDS high-risk groups. One hypothesis is that AIDS is transmitted in the same way as hepatitis - through blood products, dirty needles, fecal contamination and sexual contact.

One concern is that by the time doctors start taking specimens from AIDS victims, the pathogen that caused the disease already has left. This is particularly likely in a disease with such a long incubation period as AIDS seems to have. It is possible that the virus or whatever it is that causes AIDS enters the body damages the victim's immune system and then leaves, months before any symptoms appear.

How, then, would it be possible to ever isolate a pathogen? The epidemiologists would have to get samples before symptoms appear.

The disease is still far too rare to make random tests of apparently healthy homosexuals, on the chance that some of those tested would soon be showing symptoms. But there is one group of "non-sick" people who might be worth following carefully - homosexuals with chronically swollen lymph glands, or lymphadenopathy.

In 40 percent of the Kaposi's patients, lymphadenopathy was the first sign of trouble. The glands began to swell months before the patients realized anything was wrong.

One New York City immunologist, Dr. Roger W. Enlow of the Hospital for Joint Diseases, is following 46 homosexuals with chronic T-cell abnormalities and chronic lymphadenopathy. Enlow brings the patients in every two months, examines them, takes blood, checks some of it for T-cells and freezes the rest for subsequent re-examination if any of the patients come down with AIDS - the idea being that Enlow might catch the virus by chance, months or years before AIDS could be diagnosed.

So far, no pathogen has been seen, but five of these patients, who seemed comparatively healthy at the start of the monitoring, have since developed Kaposi's.

Despite the intense amount of research being done, the mysteries persist and the questions remain unanswered.

Why does the disease select out specific subcultures to infect, subcultures so diverse as homosexuals, IV drug users, Haitians and hemophiliacs? Is it possible that there's some sort of predisposition among the members of these groups? Testing this hypothesis, doctors at the St. Luke's-Roosevelt Hospital Center in New York studied 81 homosexuals without AIDS symptoms and discovered that more than 80 percent of them had T-cell abnormalities. This suggested to the investigators that "the number of persons at risk for serious illness may be larger than is indicated by the cases of Kaposi's sarcoma and opportunistic infections reported to date. " Many of those studied had had sexual relations with more than 100 people a year.

If sexual promiscuity increases the risk for AIDS, then why do so few women, only about 5 percent of all cases, get the disease? Dr. Joyce Wallace of St. Vincent's Hospital in Greenwich Village was intrigued by the question and studied 25 New York City prostitutes, some of whom said they had sex with several thousand men a year, frequently oral and anal sex. Wallace discovered that one of the prostitutes did have AIDS.

Why does Kaposi's sarcoma select out gays while the other diseases, including Pneumocystis, seem to strike all groups without preference? Only 18 of the 307 Kaposi's victims were heterosexual.

If AIDS is so rare, why do so many of the victims know each other? In New York City, the incidence is probably less than one AIDS victim per 1,000 homosexuals. Yet most gay victims know several people who also have the disease. One Greenwich Village writer said he personally knew 18 people who have died of AIDS.

CDC sociologist Bill Darrow has wondered about that very question and believes that AIDS is really striking a much smaller subculture within the overall homosexual subculture - a comparatively small group of very sexually active gays.

How large is the small subculture? How large is the whole gay community? What percentage of the gay community is sexually promiscuous, and what percentage is monogamous? No figures are available - only guesses based on old data, such as Alfred Kinsey's 1948 report "Sexual Behavior in the Human Male. "

The obvious explanation would be that the disease is being passed from one friend to another, but frequently there is no sexual association among these people and it is unusual, though not unheard of, for two long-term lovers to both have the disease.

Also, if the spread is person-to-person, then why are there so few cases in Philadelphia, a city with many gays who visit other gays in New York? Despite active surveillance of Philadelphia's hospitals, only eight Philadelphia residents are known to have come down with the disease so far.

Because it was only a matter of time before AIDS broke into the general population, the CDC was making a massive effort to find the cause of the disease before this happened.

No other investigation had as high a priority as this one. More than 100 persons had been assigned to the effort. And the CDC was spending more than $1 million of its $110 million annual budget in the search.

Still the mystery persisted.

For a while it looked as though the epidemic might stay confined to the four high-risk groups, but this hope was dashed before the year ended.

First, it became clear that the three hemophiliac cases were not flukes, as some of those attending the Washington meeting had hoped. Since that conference, the CDC has confirmed that four more hemophiliacs have developed AIDS , bringing the total to seven, with two other cases under investigation.

The CDC also received reports that two surgical patients had developed AIDS -like symptoms after receiving blood transfusions. Once again blood was implicated in the epidemic.

And with the approach of winter, the CDC identified its fifth high-risk group - babies.

It came as a surprise to many of the epidemiologists, but probably shouldn't have, because babies, with their still-immature immunologic systems, are highly vulnerable to unusual infections. Before the year was over, the CDC was reviewing the cases of 23 infants, all under 2. Most of the mothers were IV drug users or Haitians; one was a prostitute as well as an addict.

The CDC broke the 23 infants into two groups - 11 babies with opportunistic infections and 12 babies who seemed to be immunologically deficient but had none of the known AIDS -associated diseases.

Though all of the babies in the group of 12 are still alive, nine of the 11 infants with opportunistic infections have died.

The largest number of cases from a single institution was reported by Dr. James M. Oleske, a pediatrician at St. Michael's Medical Center in Newark, N.J., a poor city in the shadow of New York with a large population of Haitians, gays and IV drug users.

Oleske had treated eight babies - seven of them under 8 months old - with opportunistic infections, including Pneumocystis. Four of the babies died before he could do immunologic studies. But he was able to check the others and discovered that all had inverted helper/suppressor ratios.

For a long time Oleske had been suspicious that something was wrong in his community. He had been seeing an unusual number of babies with what appeared to be an immune deficiency, which is unusual in babies.

But he did not think of AIDS until the day he happened to run immunologic tests on the father of one of the babies. The evaluation was a coincidence and had nothing to do with the baby's illness; Oleske runs a lab that does all of the immunologic tests in his hospital. It was a fortunate coincidence, though, because it turned out that the father, an IV drug user, had AIDS.

The CDC is not convinced that all of Oleske's babies have AIDS , but the babies' family backgrounds are intriguing. Two of the babies are Haitian. Two were born of mothers who took IV drugs. The mother of another baby had a very active sex life with many men. And the godfather of still another baby was a homosexual, who lived in the same house, and who had AIDS.

How did these babies get sick, considering how young they were and how long the incubation period for AIDS is? Was it possible that living in the same house with an AIDS victim was enough to give a baby the disease? Was it possible that symptomatic or asymptomatic mothers passed the disease on to their children through contact or in utero?

Discovering that some babies, especially those from poor socio-economic backgrounds, were getting AIDS was understandably disturbing to the people at the CDC, charged with protecting the nation from epidemics. This development, linked to the growing number of cases either directly or indirectly related to blood transfusions, called for a forceful response from the public health officials, but what measures should be taken, what recommendations could or should be made?

The laboratories had yet to identify the microorganism that was causing AIDS , and the evidence that the disease was being transmitted through blood transfusions was, at best, only speculation.

There was no reason to even suspect blood other than the fact that some people who had received transfusions, such as hemophiliacs, also developed AIDS. There was no reason, that is, until the CDC spoke to Dr. Arthur Ammann, a pediatric immunologist at the University of California of San Francisco.

Last month, Ammann told the CDC that he had a young patient, a boy 20 months old, who kept developing opportunistic infections. A physical examination at 4 months revealed a large spleen and liver. At 7 months he was hospitalized with a severe ear infection followed by a mouth infection. At 9 months he lost his appetite, started throwing up and became jaundiced. At 14 months, he developed autoimmune hemolytic anemia - his immune system had gone haywire and was starting to destroy his own blood cells.

Immunologic studies were done. The child had few T-lymphocytes and those he did have functioned poorly. At 19 months, he developed Mycobacterium avium- intracellulare, an infection that was turning up more frequently among AIDS patients.

The baby had AIDS.

Was there anything unusual in the baby's history to explain this? Did the child have a normal birth?

No, he did not. The baby had a serious blood disorder - erythroblastosis fetalis - and was delivered by caesarean section. During the first month of his life, he had received transfusions of 19 units of blood.

Dr. Selma Dritz of the San Francisco Department of Health was contacted, and she in turn called the Irwin Memorial Blood Bank, which provided the names of the people who had donated the blood given to the infant.

One of the donors was an unmarried San Francisco businessman, 48, who said he was heterosexual. He was apparently in good health when he gave the blood.

Dr. Dritz compared the names she had gotten from the blood bank with a list of AIDS patients reported in the San Franciso area. One of the names matched. It belonged to the San Francisco businessman.

Eight months after donating the blood as an act of good citizenship, the man became fatigued and developed lymphadenopathy. He became progressively sicker and developed several infections, including cold sores, a serious cytomegalovirus infection and encephalitis. He died in August, another victim of the AIDS epidemic.

Word of the child's condition and the possibly contaminated blood transfusion was immediately forwarded to the CDC.

Within two days, the AIDS task force had notified all the key people in the investigation; conferred with the assistant secretary of the Department of Health and Human Services, Dr. Edwin N. Brandt Jr.; published the case history in the issue of the MMWR that was just going to press, and scheduled the special meeting that will be held in two days.

Even though the CDC moved so swiftly to deal with this latest development, members of the task force such as Curran and Evatt do not feel that AIDS poses an immediate threat to the nation's blood supply. But they were very concerned for the future.

Curran said the chances of anyone getting AIDS from a blood transfusion are, for the moment, small - less than the risks of not accepting a needed transfusion.

But neither Curran nor any other health official can take comfort from that for long. They are too aware of the other facts.

The number of AIDS cases has been doubling every six months. The disease may ultimately have a mortality rate in excess of 70 percent. Its cause is still unknown. There is no cure. And it seems likely now that AIDS is spreading into the general population.