In the two centuries since Edward Jenner discovered that milkmaids who had had cowpox didn`t get smallpox, medicine has ultimately narrowed the search for the source of each infection to a single microbe.
As some diseases were traced to a particular virus and others to a unique strain of bacteria, the ”one-bug” theory was confirmed again and again.
When AIDS made its first appearance among gay men and heroin users in New York nearly a decade ago, the logical assumption was that this devastating immune deficiency must also be due to a single disease-causing agent.
It began to look as though that premise was correct when, in 1983, scientists at the Pasteur Institute in Paris isolated a previously unknown strain of virus from the lymph tissue of a young Frenchman with AIDS.
Although the AIDS virus itself, now known as HIV, for human immunodeficiency virus, has still not been found in more than a bare majority of people with AIDS, up to 90 percent of AIDS patients show indirect evidence of having been exposed to it.
But as the epidemiologists obtain increasingly precise information about which Americans already are sick with AIDS or most likely to become sick, the virologists are raising important questions about the assumption that AIDS is caused by HIV alone.
The questions arise from the growing recognition, backed by now considerable laboratory evidence, that many of those who have AIDS were probably suffering from a diminished ability to fight off disease before they became infected with HIV.
Researchers have found that many homosexual men, who account for two-thirds of all Americans with AIDS, have long histories of low-grade infections that overload, or otherwise damage, the body`s immune system and leave it much more vulnerable to attack.
The other groups most ”at risk” for AIDS-East Coast heroin users, hemophiliacs, and hospital patients on both coasts who received blood transfusions before 1985-share some of the same infections, and each group also has its own unique set of what are called ”host factors,” or
”cofactors.”
”These are all people whose immune systems are really being challenged,” says Jay Levy, a pioneer AIDS researcher at the University of California in San Francisco. ”If they`ve got the AIDS virus, they`re going to have a hard time controlling it.”
If the cofactors theory is correct-and time alone will be the judge of that-it will be difficult to avoid the conclusion that a fundamental error has been made in assessing the risk of AIDS.
Until lately, the near-universal opinion within the public health establishment has been that the only thing the AIDS ”risk groups” had in common was exposure to HIV in ways most likely to cause infection.
That assumption was bolstered by studies showing that most infected homosexuals had engaged in receptive anal intercourse, which appears far more likely to spread the virus than any other form of sex.
Most heroin users with AIDS acknowledged having shared needles that were presumably infected with HIV, while AIDS patients who had received
transfusions or those with hemophilia, an inherited disease that impairs the blood`s ability to clot, had been given blood or blood-clotting factors taken from HIV-infected donors.
If the only precondition for AIDS was exposure to HIV, it seemed, then everyone exposed to HIV, including heterosexuals whose other behavior did not place them at risk, might be equally likely to fall ill with AIDS.
But a growing body of research now suggests that there are also important immunological differences, and possibly genetic ones as well, that separate gay men, heroin users and others who have AIDS from those who do not.
The possibility that, for healthy men and women, infection with HIV may not result in death or even illness, may also help to explain some of the most perplexing mysteries about AIDS.
One is why some of those infected with HIV come down with AIDS-related diseases within a few months, while many take up to five years and some have gone for nearly a decade with no signs of ill health.
Another puzzle is how to account for the appearance of fatal diseases among many AIDS patients, while others suffer nothing worse than swollen lymph nodes or even a two-week sore throat.
Because only 12 percent of AIDS patients, most of them gay men here in New York, have developed a malignant tumor called Kaposi`s sarcoma, and because its incidence is on the decline, some researchers believe that whatever cofactor is associated with AIDS and this tumor is also declining.
A third mystery concerns the small but significant number of people who show evidence of an HIV infection that later seems to disappear, as happened to several patients recently at Johns Hopkins Hospital in Baltimore.
”I believe there are people who have encountered the virus and successfully fought it off,” says Susanna Cunningham-Rundles, an associate professor of immunology at the Cornell University Medical Center in New York. ”I am very much a believer in cofactors. Isolating the virus has been to some degree a distraction, because once we`ve isolated it we felt that all we need to do is concentrate on that.”
Finally, the cofactors theory may yet provide a more satisfactory answer to the question of why, despite evidence the virus had been in existence here since the mid-1960s, the first recognized AIDS cases did not began turning up in this country until the late 1970s.
Largely lost in the public discussion about AIDS is the fact that, except for old age, few known diseases are universally fatal.
”Very few people who got the polio virus got polio,” Jay Levy says.
”One percent of the people infected with herpes (simplex) get herpes.”
Interest in the possible existence of cofactors was inspired originally by the recognition that not everyone with AIDS was dying at the same rate. Then, as various blood-testing programs around the country got underway, it also became clear that there were many more people infected with HIV than had yet become ill.
While about 21,000 Americans are currently sick with the same AIDS-related diseases that have killed another 27,000, estimates of the number of people infected with HIV range from 276,000 to 1.75 million.
In his new book on immunology, ”The Thorn in the Starfish,” Robert Desowitz, a specialist in tropical diseases at the University of Hawaii, notes, ”Those most likely to have their (HIV) infection progress to AIDS are the promiscuous gays who are already immunodepressed at the time they acquire the virus.”
Jay Levy and others caution, however, against rushing to the conclusion that healthy people are somehow ”AIDS-proof.”
”I would never want to say that,” Levy says. ”I would just say that healthy people are better prepared to handle an HIV infection than the person who does not do things in moderation and compromises their immune system.”
A multitude of factors can infringe on the body`s ability to protect itself against disease. They include such things as smoking, alcohol use and old age, drug use, malnutrition, even stress or a lack of sleep. Though the possibility remains unresolved, there is also new evidence that some people might have a genetic predisposition toward AIDS.
Among gay men, each of these cofactors may well play a role. But the most convincing case for cofactors is made by the fact that sexually transmitted diseases began showing up among gay men several years before the onset of AIDS, not just gonorrhea and syphilis but a number of viruses: infectious hepatitis, various strains of herpes virus such as herpes simplex,
cytomegalovirus and Epstein-Barr virus, even a newly discovered virus called HBLV.
Cytomegalovirus and infectious hepatitis are so common among homosexual men in cities with large numbers of AIDS cases that, before the discovery of HIV, some researchers thought those viruses might be the cause of AIDS. Epstein-Barr, the virus that causes mononucleosis, and various herpes viruses are only slightly less common.
There is particular interest at the moment in the role of syphilis as a major cofactor, stemming in part from studies showing that gay men with syphilis are four to five times more likely to progress to AIDS after infection with HIV.
Warren Winkelstein, a professor of epidemiology at the University of California and one of the stewards of a large, random study of San Francisco`s gay men, says he has a found a statistically significant association between a prior syphilis infection and AIDS.
Part of the interest in syphilis and AIDS is also due to a recent, and so far inexplicable, rise in the number of syphilis cases across the country following years of decline. Here in New York City, reports of syphilis increased by more than 100 percent during the first six months of this year, according to an article to be published in the January issue of The Atlantic magazine.
Though it is distinctly a minority opinion, a handful of researchers led by Dr. Steven Caiazza of Manhattan and the New York Native, a weekly newspaper with a large homosexual readership, have suggested that Treponema pallidum, the causitive agent of syphilis, is also the real cause of AIDS.
Largely because they are transmitted in the same fashion, the relationship between HIV and venereal diseases is not much in dispute, and many gay men also suffer from other kinds of esoteric infections.
”As a group, the promiscuous gays have more kinds of pathogenic, or potentially pathogenic, bacteria in their intestine than a Bangladeshi peasant,” Robert Desowitz has written. Pathogenic bacteria produce diseases. In 1976, three years before the first AIDS patient was hospitalized in New York, two Manhattan physicians who treated large numbers of gays in their Greenwich Village proctological practice published a landmark paper on what they named the ”Gay Bowel Syndrome.”
Beginning in the early 1970s, the two doctors reported, their white, middle-class and sexually active gay patients began to display an unusually high incidence of rectal, colonic and intestinal diseases, including nonspecific proctitis and amoebic dysentery.
Intestinal infections can result in a chronic low-grade diarrhea and malnutrition, the single most potent source of immune deficiency. Dr. James Ribilotti, one of the paper`s authors, said in a recent interview that ”quite a few” of the patients studied had since died of AIDS.
It is not only the immune systems of homosexual men that are compromised in ways that appear to leave them vulnerable to AIDS. Many of the same viral infections have been found in large numbers of heroin users, hemophiliacs and transfusion patients, even among natives of those Central African and Caribbean countries where AIDS is endemic.
Mainly because of the sharing of unsterile needles, the prevalence of infectious hepatitis and cytomegalovirus is quite high among intravenous drug users, the second-largest group at risk for AIDS. The use of opium derivatives, principally heroin, also has an impact of its own on the immune system.
Homosexual men and heroin users make up more than four-fifths of all Americans with AIDS, and while fewer than 1,300 hemophiliacs and transfusion recipients have so far come down with AIDS, both groups have their own sets of cofactors.
As what Peter Duesberg, professor of microbiology at the University of California`s Berkeley campus, calls ”lifetime recipients of exchanged cells,” hemophiliacs appear to have suffered from immune depression long before AIDS.
Because the clotting factor with which they are regularly injected is usually contaminated with infectious hepatitis and often Epstein-Barr virus, many hemophilia patients have exposures to those viruses that are equal to those of homosexuals.
Anyone who is injected with products distilled from somebody else`s blood, even if they are free of HIV and other viruses, is subjected to what researchers call ”antigen overload”-an infusion of foreign biochemicals that trigger an immune system response.
Moreover, the recent discovery that a hemophiliac`s risk of acquiring AIDS appears to run within families suggests the existence of a genetic cofactor as well.
As for transfusion patients, Jay Levy notes that most are ”under tremendous stress, because they`re usually undergoing operations. The second thing is, they`re usually not getting their own blood, they`re getting someone else`s blood. With it comes cytomegalovirus, Epstein-Barr virus, anything circulating in that blood, besides a whole host of immune cells that could start reacting against their own immune systems.”
Evidence from the Caribbean and Central Africa that the AIDS virus is apparently being passed between men and women through heterosexual intercourse has contributed much to the assumption that all Americans are equally at risk for AIDS.
But many of the same venereal and parasitic diseases that plague American AIDS patients, along with others like tuberculosis and malaria, are just as common among heterosexual adults in places like Haiti and Zaire.
What Third World nations also have in common is starvation-level poverty and the protein-calorie malnutrition that leaves residents vulnerable to many of the same opportunistic infections as AIDS patients in this country.
The last of the AIDS ”risk groups” is made up of about 600 children born to mothers who are infected with HIV, two-thirds of whom have already died. Since all newborns have vastly underdeveloped immune systems, even without any of the other cofactors for AIDS, most infants have few defenses against a virus like HIV.
Although the cofactors theory may have profound implications for the search for a prevention and a cure for AIDS, its greatest value could prove to be in helping to illuminate the origins of the disease.
It has been proposed that the AIDS virus came to the U.S. sometime in the middle 1970s, around the same time that the gay men and heroin addicts who became the first recognized American cases of AIDS are believed to have become infected with HIV.
But the recent report of a St. Louis youth who apparently died of AIDS in 1969 suggests that HIV has been present in this country for at least 20 years, and possibly longer.
Many epidemiologists now believe the AIDS virus gained its first major foothold among gay men in New York City and San Francisco, and then spread to bisexual heroin users and, through blood donations by those already infected, to hemophiliacs and hospital patients.
But as Joseph Sonnabend, a pathologist with the Uniformed University of the Health Sciences, has pointed out, ”Any hypothesis regarding the genesis of AIDS must explain the recent emergence of the syndrome. The question is,
`Why now?` ”
For Sonnabend, Jay Levy and others, it is no coincidence that the roots of AIDS infection among gay men trace back to the middle 1970s. Both researchers have cited what Sonnabend calls ”an unprecedented level of promiscuity (that) has developed during the past decade in large urban areas such as Greenwich Village.”
”This exposure to many different enteric microorganisms,” he writes,
”can create in homosexual communities . . . a situation similar to that found in nations where primitive sanitary facilities result in endemic infections.”
