The "Life-Style" Hypothesis: Experimental Work
To refine hypotheses generated by case reports, "quick and dirty" surveys, and surveillance, researchers compared patients with a group of healthy men possessing comparable sociodemographic characteristics, experiences, or behaviors. Such research designs, which begin with outcome (the disease) and attempt to discover factors retrospectively that can account for the different health status of the two groups, are known as "case-control studies." The early case-control studies were meant, in part, to test whether suspected agents like CMV or amyl nitrite might be causative factors.
One of the first such studies, by James Goedert and his colleagues at the National Institutes of Health (NIH) and the Uniformed Services University of the Health Sciences in Bethesda, Maryland, explored the relationship between KS and amyl nitrite.[32] Goedert attempted to assess the new disorder (the outcome) by collecting clinical, virological, and immunological information on two male homosexuals with KS and fifteen healthy homosexual volunteers. The researchers hypothesized that CMV hyperinfection and / or the chronic use of amyl nitrite might be causal variables. In presenting their results and assessing the implications, the investigators suggested that amyl nitrite inhalation may predispose homosexual men to immune deficiency.[33]
This investigation had some serious limitations. The small number of subjects in the study, for example, deprived it of the power to find statis-
tical significance if significance existed. Moreover, there was no internal evidence to link CMV with Kaposi's sarcoma or amyl nitrite. Though amyl nitrite was correlated with immune defects, the researchers did not report any controls for the effects of possible "confounders," that is, alternative causal variables such as the number of sexual partners, duration of homosexual experience, or any other proxy for infectious transmission of a disease. Notwithstanding its defects, the study by Goedert and his colleagues was cited by others as evidence for the plausibility of amyl nitrite as a causal variable, a tribute, in part, to the power of the "life-style" hypothesis.[34]
Almost simultaneously with the investigation by Goedert and his colleagues in Bethesda, researchers in New York City interviewed twenty gay men with biopsy-confirmed KS and forty gay male controls, matched for age and race, eliciting information on sociodemographic characteristics, medical history, sexual practices, and drug consumption. The cases were twenty of the twenty-one men, aged fifty-two or younger, with biopsy-confirmed Kaposi's sarcoma attended to by New York University Medical Center between March 1979 and August 1981. Controls were selected from the private patients of a Manhattan physician who mainly treated homosexual men. A third of those asked to be controls refused, raising the possibility that the control group was skewed in some indeterminate way. Using multivariate analysis, the investigators found that of all the study variables, only amyl nitrite and "promiscuity" (as measured by number of different sexual partners per month in the year before onset of disease) appeared to have an independent, statistically significant association with KS. The results, like those of Goedert's, were published in the Lancet , under the title "Risk Factors for Kaposi's Sarcoma in Homosexual Men."[35]
In October 1981, which was approximately when the New York City investigation began, the CDC undertook a multisite case-control study to identify risk factors for Kaposi's sarcoma and Pneumocystis pneumonia in gay men who lacked predisposing clinical factors for either. The results of the study were published in August 1983.[36] Its authors chose as controls male homosexuals without KS or PCP, matched to the cases by age, race, and metropolitan area of residence. Mindful that private-practice controls might not be drawn from precisely the same population, with equal risk of exposure to any number of factors as the cases, the researchers used, where possible, multiple controls—that is, patients from both private practice and STD clinics.
The study found that KS and PCP were associated with certain aspects of male homosexuality, in particular, numerous sexual partners per year. Other significant variables were attendance at bathhouses, a history of syphilis, the use of illicit drugs (excepting nitrites), and exposure to feces during sex. The strong implication was that a subgroup of the male homosexual population, those who were most sexually active, were at greatest risk for KS or PCP. Based on the appearance by then of similar opportunistic diseases in other segments of the U.S. population, including hemophiliacs, the authors concluded that an infectious agent might be the necessary cause.
Nonetheless, the CDC was unwilling to disengage itself from the "life-style" hypothesis or to commit itself to a microbe theory alone. In the second part of the study report, the authors summarized that position: "Although the cause of the acquired immune deficiency syndrome in homosexual men remains unknown, the study presented here and in the companion paper has identified a distinctive lifestyle as an important risk factor."[37]
In their exploration of the "life-style" model, CDC researchers asked detailed questions regarding diet, residence, drugs, and sex, then generated hypotheses based on the associations discovered. As KS and PCP were first seen in persons identified by their sexual orientation, research into sexual behavior followed logically. But the term "promiscuity" implied more than this; it implied moral judgment. Why was this term used so frequently in scientific articles? The Marmor study of 1982, for example, repeated the term "promiscuity" six times.[38]
Promiscuity denotes behavior that is casual, careless, indiscriminate, or irregular. "Irregular" means behaving without regard for established laws, customs, or moral principles, failing to accord with what is usual, proper, accepted, or right.[39] Not surprisingly, the term has been closely associated with sexuality, referring to persons who willfully violate the moral code, who lack self-control. The notion of promiscuity has been applied to groups at the "margin" of society, those who, like immigrants, the working class, the criminal, or blacks, are also seen as intemperate and prone to disease.[40]
Despite its heavy moral freight, "promiscuity" is traditionally used in medical texts to signify sexual behavior involving multiple partners. For example, in an important article in Annals of Internal Medicine in 1975, researchers reported the results of a retrospective study testing the validity of the hypothesis that serum hepatitis might be sexually
transmitted. In the monograph, five subpopulations were compared, including one composed of male homosexuals and one of male and female heterosexuals attending STD clinics in New York City. In the body of the article and in the initial abstract, both groups are described as "high promiscuity populations," although gays are singled out by the statement that "a well-known feature of homosexual behavior, primarily in men, is an extraordinary degree of sexual promiscuity," with the Kinsey work on Sexual Behavior in the Human Male cited as evidence.[41]
Other examples can be adduced. An article published in the British Journal of Venereal Disease in 1976 states that "the high proportion of homosexuality among men with syphilis and gonorrhoea has been ascribed to such factors as the promiscuous behavior of homosexuals."[42] A 1981 study in the same journal comments that "male homosexuals appear to be more prone to these [venereal] conditions than female heterosexuals because a large minority are indiscriminately promiscuous."[43]
Although it appears often in a "clinical" context, the concept of "promiscuity" retains its moral dimensions, even in a medical dialogue or text. For example, Dr. Joyce Wallace, an internist and AIDS researcher interviewed by the Journal of the American Medical Women 's Association in 1982 observed that "during the last year we have become aware of an unusual number of infections and cancers in formerly healthy homosexuals who admit to a promiscuous lifestyle."[44] She went on to say that "both monogamous homosexuals and those who are not sexually active have absolutely normal [T cell] ratios. It seems to be the promiscuity that's the culprit."[45] When asked "what does this epidemic mean?", she responded: "That promiscuity can kill you. These people don't have enough T-lymphocytes to ward off serious diseases such as tuberculosis, Pneumocystis carinii pneumonia or Kaposi's sarcoma."[46] In brief, as the title of the piece suggests ("Medical Sequelae of a Lifestyle"), the predisposing cause of the epidemic appeared to be unbridled behavior as much as a microbe or immunosuppression.
Sensitivity to the use of "promiscuity" in a clinical context was expressed in a letter to the Journal of the American Medical Association by two members of the American Association of Physicians for Human Rights, an organization consisting primarily of gay doctors. The writers noted that the use by medical personnel of a term like profound promiscuity to describe multiple sex partners was strongly judgmental. It did not belong in the scientific medical literature, and its continued use adversely affected homosexual patients, who hesitated to
discuss sexually related issues frankly with their physicians, fearing their disapprobation.[47]
"Promiscuity" as a moral expression implied that the patients bore direct responsibility for their condition. Integrated into the life-style model, the term inadvertently muddied an already difficult inferential problem; namely, whether the risk factors isolated by researchers were indirect causes of the disease, lone direct causes, or cofactors. In effect, the use of the term "promiscuity" confused a scientific problem (what factors are causally responsible? ) with a moral and political one (who is accountable? ). Perhaps more important, use of the term reflected how skewed the life-style model had become; that is, the degree to which its adherents had limited the spectrum of patients to homosexual men.
The first heterosexual patients, including the first woman, were reported by the CDC in August 1981.[48] The first clinical descriptions of immunosuppression in heterosexual intravenous drug users appeared in December 1981.[49] By June 1982 the MMWR had reported that 22 percent of patients with KS and / or PCP were heterosexuals, the majority intravenous drug users.[50] Almost a third of the heterosexual patients were women. Despite the early appearance and growing number of heterosexual patients, epidemiologic studies of this group were significantly underrepresented in the literature prior to 1984.[51]
Would investigations of heterosexual patients, paralleling those done of gays, have offered a different cast to the life-style model? We will never know for certain. The model probably would have placed less emphasis on multiple sexual partners, on "promiscuity." Perhaps chemical toxicity or the immunosuppressive power of heroin, nitrites, and other drugs might have had more significance, at least at the start. But inasmuch as women—some of whom were not intravenous drug users—were among the earliest patients, investigators might possibly have hypothesized much earlier on that a microbe was the direct cause, explaining the appearance of the new disorder in all affected groups.
Why, we might well ask, were heterosexual intravenous drug users not studied? There is no simple answer. One reason, a structural one, is that at the federal level the National Institute of Drug Abuse (NIDA) had principal responsibility for investigating issues related to intravenous drug use and had a staff of epidemiologists just for that purpose. NIDA's traditional focus, however, was only on drug abuse, eschewing investigations of diseases such as hepatitis B and endocarditis that were endemic or epidemic in their target populations. The leadership of
NIDA decided that AIDS would be treated like any other disease, thereby leaving the research initiative to other centers at NIH or the CDC.[52] Unfortunately, the CDC, lacking previous experience and expertise, shied away from studying the drug-using population, leaving a lacuna.[53]
Another reason drug users were not studied was the relatively small number of research subjects available, particularly outside the New York metropolitan area.[54] That problem was alleviated, however, by the development during the summer of 1984 of a blood test measuring antibodies to HIV. The test created a much larger pool of potential research subjects by identifying individuals who were infected but who did not have AIDS or serious, related illnesses.[55]
A final answer to the question posed was the unwillingness of epidemiologists to study this group.[56] Partly justified by the disinclination of addicts to cooperate in interviews and with follow-up, it may also, in part, be explained by a feeling among many clinicians and researchers (in this respect reflecting the attitudes of the public at large) that addicts are of less social consequence than other patients.[57] In a striking reflection of that lack of interest, at all levels of government and in the universities few epidemiologists had expertise in drug addiction when the HIV epidemic began.
Despite its appeal, the life-style hypothesis was eventually undercut as a sufficient explanation. During 1982 epidemiological surveillance and case reports made it clear that in addition to homosexual males, others were at risk for AIDS. As an article in JAMA observed in September of that year: "If lifestyle is the key, the question still remains: Why has AIDS also occurred in heterosexual men (84 cases so far), women (32 cases so far), mostly heterosexual Haitians, and hemophiliacs?"[58] A new model was required.