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Posted: 24 May 2011
30 years in 30 weeks, 1984

Categories: careers, opinion piece

Discovery of a new retrovirus in AIDS patients quickly led to the development of virus detection assays, which were crucial for two reasons: First, they provided the means to confirm the hypothesis that HIV was the etiologic agent of AIDS. Second, these sensitive detection assays were used to screen the blood supply for the presence of HIV, thereby eliminating an important route of HIV transmission. While the number of deaths from AIDS continued to rise and AIDS cases were reported in Europe and Africa, there were reasons for optimism. The underlying cause of the disease was identified and with this finding came the possibility that ways to control the disease would soon be found. One of the most active laboratories working on the newly discovered virus was led by Dr. Gallo, who, in his commentary, goes back to those years and the several papers that his lab published in 1984.

Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-111) from Patients with AIDS and Pre-AIDS

Science 4 May 1984: Vol. 224 no. 4648 pp. 497-500 DOI: 10.1126/science.6200935

M Popovic, MG Sarngadharan, E Read and RC Gallo

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1983 < All years > 1985

Commentary by Dr. Robert Gallo

The paper was one of four published by my lab in early May in Science.  Collectively, these papers, along with one in June 1984 in Lancet, convinced the scientific community that HIV (then called HTLV-III) was the cause of AIDS.  We described the technique and results of the HIV blood test as well as made available HIV-producing cell lines, and other reagents for the global scientific community.

Our paper in Science described frequent detection and short term culture of HIV from 48 patients with AIDS or in people with conditions defined by CDC as at great risk for AIDS; no virus was detected in blood cells obtained from 115 healthy heterosexuals.  Because of the great difficulties in isolating HIV at the time, due to the low number of T cells in blood of AIDS patients and the very limited number of virologists accustomed to culturing human T cells with interleukin-2 (IL-2), I believed verification would be painfully slow.  Consequently, my colleagues and I realized that a safe, simple, sensitive and accurate HIV blood test was not only necessary for stopping transmission of HIV by blood transfusions, but would be essential for proving causative association between HIV and AIDS. The blood test was the main point of two of the five papers.

A blood test was made possible by work described in the Science paper “Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDs and Pre-AIDS” by Popovic et al.  In this paper my co-workers and I described a system for reproducible isolation and continuous culture of “pathogenic variants” of HIV (later called X4 variants) in clones of neoplastic CD4+ T cell lines. This system enabled sufficient amount of HIV to be produced for the HIV blood test. We also described  the technique of using these cells for routine detection of HIV by testing for induction of giant multinucleated cells.

My research was inspired by my belief that I could help solve the question: What was the cause of this new disease?  With my co-workers I had just discovered and isolated the first human retrovirus called HTLV-1 (1980) and with others showed it was a cause of some adult T cell leukemias.  In 1981-1982 we discovered a second human retrovirus - HTLV-2.  In early 1982, I was stimulated by a lecture by James Curran, then at the CDC.  He described a new disease (AIDS) and fears of it becoming a pandemic.  He asked for help from virologists. I believed AIDS might be caused by another (the 3rd) human retrovirus based on the facts that: HTLVs were targeting CD4 + T cells; they were transmitted by blood, sex and mother to infant; and they could cause minor immune impairment.  All these properties fit what might be the characteristics of an AIDS virus, except the immune impairment was very severe and that could be from differences in the envelope protein as has been seen for envelope variants of feline leukemia virus. So we began part-time work on AIDS in May 1982, but much more intensively in 1983.

There was one significant early surprise and later another.  It had taken us several years to convince the scientific community of the existence of human retroviruses (HTLVs).  HTLV-1 and 2 belonged to a definite, related group. We assumed HIV would be in the HTLV family, closely related to HTLV-1 and 2, but perhaps with a significant variation in envelope. Instead, HIV belongs to a distinct group. This was a surprise to me.  A second surprise caused a problem and much confusion.  We had succeeded in growing several isolates of HIV in continuous culture.  One grew best so we selected it for the blood test, but it seems that this isolate (HTLV-3B or simply 3B) was contaminated by the virus sent to us from the Paris group. It was known as “LAV”. Confusion increased when we discovered LAV could not grow in cell lines. It appears that Montagnier had first contaminated LAV with a virus from another patient (LA1), and unwittingly sent LA1 to us, because we had asked for more LAV, as the original LAV sent to us had proven to be impossible to work with. The confusion was made worse by my decision to have my co-worker, Sarangadharan, give HIV-3B, growing in a T-cell line to Montagnier in the spring of 1984.

In any event, this seemingly trivial problem (both labs had other independent isolates, and we had several in continuous culture) provided fodder for the resultant legal attacks in an effort to obtain substantial sharing of the royalties on the HIV blood test that was awarded to the U.S.

About the author: Dr. Robert Gallo is the director of the Institute of Human Virology at the University of Maryland School of Medicine.

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