English Version
Progress in scientific research rarely follows a straight path. Generally, it entails many unexpected meanderings, with a mix of good and bad ideas, good and bad luck. The discovery of the human immunodeficiency virus (HIV) as the cause of AIDS did not avoid this pattern.
The story began in an unfavorable environment: during the late 1970s, many people thought that epidemic diseases caused by microbes, including viruses, no longer posed a threat in industrialized countries. Other prevailing beliefs were that viruses did not cause any human cancers and that there was no such thing as a retrovirus that infected humans. Some of these beliefs were justified, since attempts to find tumor viruses and, in particular, retroviruses in cancers or other diseases in humans had a troubled history, and many of the groups that had the greatest expertise in the study of retroviruses had turned their efforts toward research on oncogenes. Luckily and rather amazingly, however, the conceptual and technical tools arrived in our hands just before the first patients with AIDS were identified in 1981. In addition, there remained a few heretical or “old-fashioned” groups — among which were our two laboratories — that persisted in searching for retroviruses in human cancers, particularly breast cancers and leukemias. This search finally paid off with the discovery of human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2), the first of which was shown to cause an unusual T-cell leukemia. This discovery was made possible by 15 years of basic research on leukemogenic retroviruses in animals, including the design and development of highly sensitive biochemical assays that were based on reverse transcriptase — the enzyme that is present in all retroviruses, which was discovered in 1970 by Temin and Baltimore.
The story began in an unfavorable environment: during the late 1970s, many people thought that epidemic diseases caused by microbes, including viruses, no longer posed a threat in industrialized countries. Other prevailing beliefs were that viruses did not cause any human cancers and that there was no such thing as a retrovirus that infected humans. Some of these beliefs were justified, since attempts to find tumor viruses and, in particular, retroviruses in cancers or other diseases in humans had a troubled history, and many of the groups that had the greatest expertise in the study of retroviruses had turned their efforts toward research on oncogenes. Luckily and rather amazingly, however, the conceptual and technical tools arrived in our hands just before the first patients with AIDS were identified in 1981. In addition, there remained a few heretical or “old-fashioned” groups — among which were our two laboratories — that persisted in searching for retroviruses in human cancers, particularly breast cancers and leukemias. This search finally paid off with the discovery of human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2), the first of which was shown to cause an unusual T-cell leukemia. This discovery was made possible by 15 years of basic research on leukemogenic retroviruses in animals, including the design and development of highly sensitive biochemical assays that were based on reverse transcriptase — the enzyme that is present in all retroviruses, which was discovered in 1970 by Temin and Baltimore.
An additional important contributor was the development of methods for growing T lymphocytes in culture for a period sufficient to allow the expression of putative latent retroviruses. This effort was helped greatly by the isolation of specific factors in particular, the T-cell growth factor (now called in terleukin) in Bethesda, Maryland. The role of interferon in repressing the production of retroviruses in mouse cells was demonstrated in Paris, and this discovery led to the use of anti-interferon serum in the search for human retroviruses. Thus, at the beginning of the 1980s, we had the essential tools required to search for a retrovirus in this new and menacing disease called AIDS. But why search for a virus, and specifically a retrovirus, in AIDS? The answer was far from obvious in 1982.
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