"Strong Evidence of a Causative Involvement"
Certainly one of many unusual aspects of the whole affair was that Heckler's press conference was held before Gallo's findings had even been published in a peer-reviewed forum—normally a serious breach of professional scientific etiquette in itself. Those who wanted more substantial information about Gallo's claims had to wait until May 4, when four articles by Gallo's group appeared in the pages of Science . This too was extraordinary. As Gallo later commented, "Getting one paper in Science is a lot. Getting two is fantastic. Getting three was a record. We had four at one time."
Gallo used these articles to put forward a series of interconnected claims: that he had found a new virus; that he had succeeded in mass-producing it; that the virus was related to HTLV; that antibodies to the virus could be detected in blood; and, most crucially, "that HTLV-III may be the primary cause of AIDS." In the second of the four papers, Gallo and his coauthors focused specifically on the etiological argument. After reviewing the evidence in favor of an infectious agent as the cause of the syndrome, Gallo reminded his readers that "we and others have suggested that specific human T-lymphotropic retroviruses (HTLV) cause AIDS." Gallo's wording was also significant: he had redefined HTLV, from "human T-cell leukemia virus" in 1983, to "human T-lymphotropic retroviruses " in 1984. While the original name denoted the relation between a single retrovirus and a specific form of cancer, the new name described a family of viruses more vaguely characterized as "T-lymphotropic," that is, having an affinity for T cells. Gallo had reinvented "HTLV" so as to more plausibly encompass his new virus as a relative of HTLV-I and HTLV-II.
Moving on to HTLV-III, Gallo described detecting the virus in, and isolating it from, "18 of 21 samples from patients with pre-AIDS [the so-called lymphadenopathy syndrome], three of four clinically normal mothers of juvenile AIDS patients, three of eight juvenile AIDS patients, 13 of 43 … adult AIDS patients with Kaposi's sarcoma, and 10 of 21 adult AIDS patients with opportunistic infections." Although
ideally one would expect to find a primary causative agent in every case of a disease, Gallo noted that "the incidence of virus isolation reported here probably underestimates its true incidence since many tissue specimens were not received or handled under what we now recognize as optimal conditions." In contrast with these findings that associated the virus with the expression of AIDS was the striking absence of HTLV-III in cases where AIDS was also absent. Out of 115 clinically normal heterosexual blood donors, not a single one showed signs of the virus. And out of 22 clinically normal gay male donors, only one tested positive for the virus, and that person developed AIDS within six months. These studies, Gallo and his coauthors concluded, "provide strong evidence of a causative involvement of the virus in AIDS."
What in fact had Gallo established? Four years later, in response to challenges about whether the virus had been proven to cause AIDS, Gallo would maintain: "In my opinion all of the sufficient data was available at the time the cause was first announced in the spring of 1984." But this was a difficult position to sustain, at least on the basis of Gallo's published findings. Gallo had shown that, in specific small samples, laboratory signs indicating the presence of his virus were often correlated with the expression of AIDS at what were believed to be two different stages of disease progression ("pre-AIDS" and AIDS). Moreover, there were no such signs of virus in clinically normal people, suggesting that the virus or viruses had some special relationship to AIDS. But just because HTLV-III and LAV were often correlated with the syndrome, did that mean they were causing it? AIDS, after all, was a syndrome whose hallmark was the presence of a range of opportunistic infections; perhaps HTLV-III and LAV were viruses that were contracted by people who already had weakened immune systems. Gallo would have been in a better position to respond to this challenge if he had had more cases like that of the clinically healthy but infected gay man who later developed AIDS. But the other 21 of his 22 "clinically normal homosexual donors" all tested negative for the virus, so there was really no evidence that HTLV-III infection was a precursor to immune system damage. (Three out of 4 of the "clinically normal mothers of juvenile AIDS patients" tested positive for the virus, but these numbers were small, and Gallo did not report that any of the women had subsequently developed AIDS symptoms.)
When asked ten years afterward whether he had been able, at
the time of publication, to rule out the possibility that HTLV-III was an opportunistic infection, Gallo acknowledged that he could not. But "the evidence was overwhelming in my mind," Gallo recalled. "Science is never 100 percent. It's not mathematics. You play not on hunches, but on data that becomes overwhelming in your mind. …" To make a credible claim for "strong evidence of a causative involvement," Gallo was in fact relying heavily on the plausibility of HTLV-III as a pathogenic agent, given what was known about the virus and about AIDS. At least in vitro, HTLV-III killed helper T cells. And the central manifestation of immune system damage in people with AIDS was precisely the low numbers of those same helper T cells. Still, at this point, little was known about the effects of HTLV-III in vivo.