Gallo's Family of Viruses
Writing in 1988, Robert Gallo, the NIH scientist who would share credit for discovery of what was to become known as the "human immunodeficiency virus," reflected back on the scientific effort to understand AIDS. Gallo concluded that progress had been made possible by "two general earlier developments": "first , by major advances that took place in basic sciences, particularly in immunology
… and molecular biology …; and second , by the opening of the whole field of human retrovirology that, oddly enough, occurred only a few years before the AIDS epidemic. …" To this Gallo added, "There is no doubt in my mind that if AIDS came upon us full force in the 1960s or even in the early 1970s, we would still be wandering in the dark regarding most of what we know today."
Gallo's "odd" fact can be put in different terms: At the moment when people began to suspect that AIDS might be caused by an infectious agent, there existed a small group of prominent scientist working in a very specialized area who were inclined to imagine that a "retrovirus" might be the cause, who were motivated to pursue that speculation, and who were well equipped to do so. Only in the 1960s had researchers discovered that the genetic material of certain viruses consists of RNA (ribonucleic acid) rather than DNA (deoxyribonucleic acid, often called the "blueprint of life"). Normally, viruses infect cells and turn them into virus factories, causing the cells to produce new viruses according to the specifications of the rival DNA. The virus's DNA is copied into RNA, which is then used to manufacture viral proteins; once the new viruses are assembled, they are ejected and go off to infect other cells. When viruses were found that consisted of RNA rather than DNA, they presented a puzzle to scientists, because it was unclear how the viruses could replicate. In 1970, however, in work that would win them the Nobel Prize, researchers David Baltimore at the Massachusetts Institute of Technology and Howard Temin at the University of Wisconsin independently discovered that these RNA viruses contained an enzyme, which they termed "reverse transcriptase," that copied the viral RNA into DNA. This DNA then served as the blueprint for the manufacture of new viruses. So while in normal viruses the sequence was "DNA to RNA to new viruses," in these unusual viruses there was an extra step: "RNA to DNA to RNA to new viruses." To describe the transcription from RNA to DNA and back again, virologists coined the term "retrovirus."
During the "War on Cancer" in the 1970s, researchers such as Gallo at the NIH's National Cancer Institute (NCI) investigated links between animal retroviruses and various forms of cancer. However, until the late 1970s, no retroviruses were known to cause disease in humans. At that time, both Gallo and a group of Japanese researchers claimed credit for the discovery of one believed to cause adult T-cell leukemia, a rare form of cancer found mostly in Japanese fishing villages. Gallo named the retrovirus the human T-cell leukemia virus,
or HTLV. This work earned him the Lasker Prize, the highest award in biomedicine short of the Nobel Prize. He found another virus in the same family in 1982, which he claimed caused a different type of leukemia; in consequence, the two viruses became known as HTLV-I and HTLV-II.
As Gallo described it in retrospect, when he first heard about the new syndrome in gay men in 1981, he had no reason to think it might be linked to a retrovirus and indeed had little interest in the issue. Or as Joan Fujimura has suggested more generally, scientists construct and pursue "do-able problems": they do not venture off in any direction at random, but rather structure their work by finding effective ways of integrating and coordinating the relationship between the experimental procedures at hand, the organization of their laboratories, and the social worlds through which they move. Given that the initial hypotheses focused on homosexual lifestyle risks, many virologists simply saw no particular reason to be interested.
By Gallo's account, his curiosity was piqued only in 1982, when James Curran of the CDC briefed NIH researchers about the epidemic, expressing to them his own belief that the syndrome was caused by an infectious agent, and stressing that one hallmark of the syndrome was the helper T-cell deficiency. This was enough for Gallo to hypothesize that the epidemic might be caused by HTLV or by a retrovirus of the HTLV family—by a close relative, that is, of the two viruses whose discovery had already brought him considerable acclaim within the world of virology. After all, HTLV specifically infected helper T cells; moreover, HTLV was known to be transmitted in blood and semen, which seemed also to be plausible transmission routes of the putative agent in AIDS. Finally, there was some precedent for a retroviral role in a condition like AIDS, since a feline retrovirus was linked to immune deficiency in cats. Gallo became convinced that AIDS was an HTLV-linked disease. Only some years later would he do an about-face and make an intriguing confession: "That hypothesis, as it turned out, was wrong. Nonetheless, it was fruitful, because it stimulated the search that led to the correct solution."
Gallo had little patience for alternative hypotheses that were common at the time. The medical tendency to, as he put it, "round up the usual suspects"—CMV, Epstein-Barr virus, and the like—seemed to him unlikely to provide an explanation for what was, after all, a new epidemic. Nor was he impressed by the popular hypothesis of immune overload. Interestingly, he objected not just on empirical grounds—that
immune overload seemed unlikely to account for manifestations in all the risk groups—but also on the basis of his understanding of causality in disease processes: "Whereas some complex diseases … are believed to involve different steps and sometimes different factors, most human disease (even some cancers) can be thought of as involving a primary causal factor. Certainly this has been the case for most past epidemic disease for which we in time did learn the cuase."
Committed in general to what Dubos called the "doctrine of specific etiology," Gallo dedicated his laboratory to an investigation of his hypothesis: that AIDS was caused by the virus he was already working with and had invested in, HTLV. Within weeks of embarking on this search, Gallo's assistants found the leukemia virus in the T cells of two U.S. gay men, a Haitian woman who died of AIDS in France, and a Frenchman who had received a blood transfusion. Gallo sent two papers describing the findings to Science magazine, the preeminent general science publication in the United States. His colleague, Myron ("Max") Essex at the Harvard School of Public Health, sent along a third paper also reporting signs of HTLV infection in AIDS patients.