Impure Science: AIDS, Activism, and the Politics of Knowledge. Epstein S. 466 pages. Berkeley: Univ of California Pr; 1996. $29.95. ISBN 0520202333. Order phone 800-822-6657.

In a recent piece in The New York Times [1], prominent AIDS researcher Max Essex and epidemiologist Bruce Weniger argued that two things intrinsic to the culture of the National Institutes of Health (NIH)-the high premium placed on basic as opposed to applied science and the risk-averseness associated with a large bureaucracy-made the NIH the wrong place in which to develop and test HIV vaccines. This type of postmodern spectacle-prominent scientists using cultural arguments in the lay media to influence scientific and public opinion about important scientific policy and public health issues-is now so common that it draws no special attention. Do such public negotiations suggest a breakdown in the autonomy and authority of science, greater democracy in scientific decision making, both, or something else? How has this situation come about? Is it good or bad? Two recent books, which look at seemingly disparate medical controversies from very different angles, offer answers to these questions.

Marcia Angell, executive editor of The New England Journal of Medicine, took a leave from her editorial work to write Science on Trial: The Clash of Medical Evidence and the Law in the Breast Implant Case, an account for a general audience of the controversy over whether breast implants cause connective tissue disease. Angell was in a good, but by no means disinterested, position from which to observe this story, having written an editorial in 1992 criticizing then U.S. Food and Drug Administration (FDA) Commissioner David Kessler's decision to ban breast implants and having overseen the later publication of two largely negative case–control studies on breast implants and connective tissue disease [2-4]. She gives a clear and concise account of the FDA ban, prominent court cases, scientific data, and media reaction. She convincingly argues that no epidemiologic data support a more than minor association between breast implants and any specific autoimmune disorder. Most readers will share Angell's dismay that juries have nevertheless awarded large monetary settlements against implant manufacturers and that many persons continue to believe that implants cause connective tissue disease.

Steven Epstein, a sociologist at the University of California at San Diego, has reworked his doctoral dissertation on the controversies over the causes of AIDS and the role that AIDS activists have played in influencing regulatory, research, and clinical policies into a book for a wider audience: Impure Science: AIDS, Activism, and the Politics of Knowledge. Epstein paints a decidedly nonjudgmental picture of how various AIDS-related controversies have played out. His central observation is that scientists and AIDS activists have borrowed techniques and knowledge from each other in the ultimately social and political task of advancing their own (sometimes overlapping) interests.

Credibility, Authority, Evidence, Objectivity

Although Angell begins her book by promising to answer the crucial question that underlies the implant controversy, "What are the essential distinctions in the way science, the law, and the public regard evidence and what are the consequences for our society?", she seems more interested in arguing that science is the single, correct way to find and validate evidence than in exploring other perspectives.

The core of Angell's argument is that the FDA, the judicial system, physicians testifying for plaintiffs, the media, and organized patient advocacy have ignored the scientific evidence against a causal connection between implants and connective tissue disease. Angell does not question whether particular values and interests may have shaped the way in which scientists produce, legitimate, or classify evidence. "Whether silicone-gel-filled breast implants cause connective tissue disease is not ultimately a matter of opinion or legal argument," Angell declares, "it is a matter of biological fact."

Even if we restrict our focus solely to the issue of implants, Angell's major assumption-that scientific evidence, such as the results of the epidemiologic studies of breast implants published in The New England Journal of Medicine, is value-free and objective-is problematic. First, the thresholds set by biomedical researchers for statistical significance and power, as well as decisions about the magnitude of effect that is clinically significant, are value judgments. For example, one of the studies that Angell reviews determined that breast implants were associated with a relative risk for connective tissue disease of 1.24, a value with a 95% CI that did not include 1 [5]. Some could legitimately perceive this risk as real and important, although I agree with Angell's analysis that the degree of overall implant-associated risk, if real and not the result of overreporting or selection bias, has only a minor effect on the health of women. One has only to look at such controversies as that over screening mammography for women in their forties to see that relatively small inconsistencies and ambiguities in medical evidence permit, but do not cause, intractable debates among different groups within the scientific community.

Second, biomedical scientists often choose to ignore or give less emphasis to data that are inconsistent with the larger body of evidence or with their values and interests. Angell, of course, is very aware of the complexities of interpretation and does an excellent job of discussing the basic principles of clinical epidemiology and critical appraisal and how they apply to the evidence about implants. She invokes philosopher of science Karl Popper to stress that new evidence needs to be evaluated in light of existing knowledge and that causal and other theories should be formulated in such a way that they can be proven false. My only objection is that we should not use this unrealized ideal to argue for reforms, such as allowing only court-appointed neutral experts to testify. Rather, we should judge reforms against the ways in which biomedical researchers typically evaluate evidence in controversial situations. Unlike the Popperian ideal, the evidence in many medical controversies is often messy and inconsistent enough to allow different sides to disagree about what counts as evidence sufficient to challenge preexisting opinions.

And we must not forget that what counts as a scientific controversy in the first place is largely driven by social forces rather than by scientific evidence. One of the remarkable features of the implant controversy is what it is not about-there seems to be little controversy or public worry over the "known" ill effects of silicon gel implants, such as ruptures, leakage, contractures, and difficulty with mammography. My guess is that it is not the greater potential health effects of "connective tissue disease" that explains this condition's centrality in this controversy but rather its vague definition; its potential for serious, late manifestations; and its connection with the immune system, all of which make it more anxiety provoking.

Third, and most relevant to clinicians, Angell does not grant any validity or sympathy to those who question the tight connection between "there is no good epidemiologic evidence for this" and "this is not real." A recent television documentary contained a stunning visual image: a rally of implant activists chanting "we are the evidence" [6]. These activists were saying, in effect, that medical evidence pointing to a similar frequency of connective tissue disease-like symptoms among persons without implants could not invalidate their own suffering, which they knew from experience was real. Epidemiology, working from a population perspective, speaks about aggregate associations between specific exposures and specific mechanisms and abnormalities. The absence of an association between implants and connective tissue disease does not rule out an association between implants and other health consequences, nor can it make us certain about what is true in any particular individual person. And, perhaps most profoundly, why should suffering be legitimate only if it is the result of an underlying pathophysiologic abnormality? Although I agree with Angell that what matters in determining the legal liability of implant manufacturers is the aggregate data, when it comes to the care of women who come to clinicians fearing breast implant-induced disease (about which Angell has little to say), these epistemologic concerns are of central importance.

Finally, Angell's defensive rhetoric about the objectivity of scientific objectivity is undermined by the story she tells. The charge that most galls her and seems to her to be the most egregious example of lay cynicism toward science is that the negative studies published in The New England Journal of Medicine were tainted because they were funded in part by a professional organization of plastic surgeons and implant manufacturers. Angell finds this charge ludicrous, noting that strict rules of disclosure and peer review protect against biased science and interpretation.

But Angell does not give enough attention to the fact that neither disclosure policies nor peer review can protect us from the ways in which corporations and others with deep pockets can guide researchers or institutions to study particular questions, and not others, at specific times. As Angell critically documents, the 1992 FDA ban on breast implants, the early large court cases against the implant manufacturers, and the large class action settlement all occurred before the publication of any relevant epidemiologic studies. In addition to the fact that the safety of the implants did not have to be proven because the implants were "grandfathered" into FDA regulations about medical devices, Dow Corning and other manufacturers, before the controversies of the 1990s, had little economic interest in funding epidemiologic studies that might raise questions about devices that were generally thought to be safe. As rational actors, these manufacturers chose not to fund large observational studies until it was in their interest to do so. Once they decided to fund research, they had the potential to influence the debate by choosing to sponsor medium-sized, observational trials that they might have surmised were unlikely to find significant associations between implants and disease. Although it may be an objective biological fact that implants do or do not cause disease, if and when and how such facts are "discovered" can certainly be influenced by money.

Compared with Angell, Epstein has a more contingent view of evidence. He documents ways in which scientists and regulatory officials evaluate and legitimate evidence every day by making social judgments about the authority and credibility of sources of evidence (these observations are similar to Angell's observations in the courtroom). This is not an antiscience view, it is an empirical, scientific view of science based on the ways in which scientific controversies are actually constructed and played out rather than on an idealized notion of how science should work.

Epstein picks an extreme example of scientific credibility, the "Duesberg heresy," to study how credibility figures in the evolution of a biomedical controversy. Peter Duesberg is a molecular biologist at the University of California, Berkeley, who has impeccable scientific credentials. Since 1987, he has argued that AIDS is not caused by HIV. In Duesberg's view, HIV infection is another opportunistic infection-a consequence, not a cause, of AIDS.

Epstein uses the Duesberg heresy as a kind of social assay of the elements that make for scientific consensus about cause. In Epstein's view, the idea that HIV causes AIDS quickly became an orthodoxy in the mid-1980s, even though medicine's own metaprinciples of cause, Koch postulates, were not satisfied (and continue not to be satisfied) and even though there was and is reason to believe that other factors might be necessary for transmission and infection. The idea that HIV causes AIDS was, in Epstein's sociological terminology, quickly "black-boxed" into a fact, erasing uncertainties.

Duesberg has been able to use his scientific credentials to attract media attention (the media have, at times, depicted him as a present-day Galileo challenging the scientific church) and to build alliances with individual persons and groups suspicious of biomedical authority. He has made use of a set of often contradictory arguments and speculations, from the inherent limitations of monocausal theories of any infectious disease to the lack of democracy in science. Although I have no doubt that Duesberg's hypothesis is wrong, I agree with Epstein that it is the very attack on a quickly congealed scientific consensus by an insider with impeccable credentials that explains both the violent negative reaction to Duesberg and the great amount of publicity that has been generated.

Epstein's narrative is also full of examples of the ways in which money and power influence what gets studied and when. He cites the way that Burroughs Wellcome, the manufacturer of zidovudine, facilitated research trials of zidovudine in combination with other products that it manufactures, such as acyclovir, but dragged its feet in creating the conditions in which zidovudine might be studied with interferon, a product of another company.

Lay Activism: Acting Up or Acting Out?

The unavoidable reality for AIDS activists has been the ultimate dependence of the critic on the criticized. The dependence on science for new drugs, fundamental research into the pathogenesis of AIDS, and good medical care has led to a paradoxical schism between advocates' often virulent, antiscience rhetoric and their pragmatic engagement with clinicians, scientists, and policymakers.

Epstein documents how AIDS activists have been able to influence the scientific establishment, especially with regard to changing the ways in which drugs are regulated and clinical trials are conducted. First, AIDS disproportionately afflicted gay men, a group that already had a social and political identity and that included many persons with considerable political experience. Second, AIDS groups gained legitimacy, credibility, and sympathy because the disease was ravaging their bodies. Third, AIDS activists recognized and exercised their collective power to influence research by choosing to participate in or rally against clinical trials. Finally, AIDS activists did their homework: They learned about the inner workings of regulation and clinical research and made alliances with the insider critics of the biomedical status quo.

To take the most important example, AIDS activists lobbied for less stringent exclusion criteria for clinical trials, motivated by the desire to gain greater access to experimental treatments. They found a receptive audience in many epidemiologists and biostatisticians who also criticized the holy grail of randomized, placebo-controlled clinical trials-for using variables that were easy to measure and manipulate rather than those derived from clinical experience, for producing results that are difficult to apply because of the homogeneity of study populations and the use of clinical settings that are hard to replicate, and for being ethically suspect in their use of placebo groups.

Epstein documents the pragmatism of many AIDS activists, which led to temporary and unlikely alliances. When it came to removing bureaucratic obstacles to bringing drugs to the market, AIDS activists found allies in conservative critics of any and all federal regulation. Epstein chronicles the toll that this constructive engagement between lay advocates and science had on its participants. For activists, he writes, "organizing a social movement is arduous enough without having to learn oncology in your spare time." And more radical elements charged that those who participated in policymaking and dialogues with mainstream scientists had sold out. On the opposite side, regulators, researchers, and clinicians who actively cooperated with activists were accused by peers of corrupting "pure" science.

In Epstein's view, AIDS activists contributed to constructive changes in clinical research and drug regulation. Angell, in contrast, sees little constructive engagement between mainstream science and patient advocacy groups in the implant saga. She views lay advocates as, at best, victims of unscrupulous lawyers, cowardly regulators, and sensationalist media. At other times, she stresses the financial bonanza that was associated with legal settlements and the sleazy alliances between trial lawyers and some patient advocacy groups. Lay ignorance of science is the fundamental problem, she contends, and should be corrected by mass education and the use of neutral experts in the courtroom.

Angell does emphasize one silent lay voice in the implant debate: women who have been denied implants as a result of Kessler's 1992 ban. Kessler's decision was based largely on a risk–benefit calculation made in great ignorance-a theoretical risk for connective tissue disease balanced against the benefit to women who wanted breast augmentation (reconstruction after cancer surgery was and is another matter). If one presumed that breast augmentation had little value, one could make a regulatory decision based on a very low threshold of risk. Angell rightly takes Kessler to task for the paternalism inherent in judging that many women didn't really need implants. She is understandably vexed by attempts to frame the statement "implants cause connective tissue disease" as a feminist cause.

I fully agree with Angell's criticism of the FDA's paternalism, but I find fault with the larger moral that she draws. Angell finds it reprehensible that in banning the implants in 1992, "the FDA responded like a political body, not a regulatory body" and that "the FDA was supposedly not taking a sociologic stand, but a regulatory one." Why is characterizing FDA decision making as political or sociological so damning? How could this process of balancing competing values and interests, especially during a period when little epidemiologic data were available to guide decision making, not be at least partly political and social?

Pure or Impure Science?

There are, of course, many differences in the biological and clinical realities underlying the AIDS and breast implant controversies that may exaggerate the gulf between the points of view of these two authors. Perhaps the most important difference is a fundamental lack of sympathy among many persons inside and outside of medicine for an "invisible disease" brought on by women who chose breast implants for "cosmetic" reasons. To many, such women are not victims of anything other their own anxieties and guilt. Both Angell and Epstein also acknowledge that complicated social negotiations between and among scientific insiders and outsiders lead to changing concepts of, names for, treatments for, and policies about diseases.

Nevertheless, Angell and Epstein find very different meanings in these negotiations. Epstein finds a constructive engagement between outsider and insider that improves science and scientific policy at the same time that it makes science more democratic. He sometimes overstates these beneficial effects and does not distinguish clearly between the instances of constructive engagement and the often self-defeating antiscience, essentially anti-intellectual, rhetoric of many activists. Most scientists hold deeply felt beliefs, whether true or not, about the "purity" of their work. The AIDS activists may have had even more success if they had used a kinder, gentler rhetoric.

Angell issues no call for greater democracy or lay participation in science or scientific policy. If anything, she makes the implant story into a case study of how the law, the media, and patient advocacy mangled something that should have been left to scientists alone. I think she is too idealistic in proposing that we rededicate ourselves to the objectivity, neutrality, and autonomy of science. Like the antiscience rhetoric of many lay advocates, the spirited defense of scientific purity-and the inevitable moralizing tone that accompanies it-may only stoke the flames of misguided "culture war" debates and alienate the many persons whose suffering remains nameless and illegitimate.