To the editor:

I appreciate the efforts of Nature Medicine, in its July 2003 issue, to maintain awareness of the growing HIV/AIDS problems in the world, as well as its celebration of the twentieth anniversary of the first isolation of HIV.

In seeking to ensure that lessons may be learned from the international collaborative efforts to identify the cause of AIDS, it is important that the historical record remains accurate. This is why I wish to correct and elaborate on the recent commentary by my former collaborator, Françoise Barré-Sinoussi1. In particular, I believe readers may have been confused by statements regarding the timing of events and roles and responsibilities of the participants, especially if they compare her version of the 1983 events at the Pasteur Institute to my own published reports2,3. I realize that some details of this collective work may have faded from the memory of its contributors; however, original documents such as laboratory notebooks and earlier eyewitness accounts remain available.

The statement by Barré-Sinoussi that “we were convinced that we were dealing with a new retrovirus” should be viewed more as a sequence of events. Our group at the Pasteur Institute, which initially included myself as founder and head of the viral oncology unit, Jean Claude Chermann as laboratory chief and Françoise Barré-Sinoussi as research associate, was looking for a virus like human T-lymphotrophic virus (HTLV). This had already been suggested by Robert Gallo and was first proposed to us by Jacques Leibovitch and Paul Prunet from the Pasteur Institute. Besides immunofluorescence, a key experiment in elucidating the nature of the reverse-transcriptase activity in the medium of the first culture (BRU) was the specific immunoprecipitation of a 35S-labeled 25-kDa protein (now called p24Gag) by patient serum and not by antibodies to HTLV p24. It was only when our putative retrovirus did not react with the HTLV antibodies that we realized that it was a new kind of retrovirus.

The initial clinical isolate, unlike HTLV, had no transforming or cytopathic effects on T lymphocytes. Barré-Sinoussi notes in her commentary that the lymphocyte culture I started from the patient's lymph node biopsy died after 4 weeks. But this was anticipated as soon as we realized that the cells were not transformed, because normal cultures of the same type also die within this time period. The need for succesive use of peripheral blood mononuclear cells to maintain a viral culture was therefore a likely hypothesis that proved to be correct. The virus would later be classified as non-syncytium-inducing, as is usually the case for viruses isolated from recently infected HIV patients who are either asymptomatic or present with lymphadenopathies. However, the first typical cytopathic effect, formation of large syncytia, was not observed until 5 months later, in a third clinical sample (HIV LAI) from a patient who had full-blown AIDS. The figure in Barré-Sinoussi's commentary refers to this third clinical isolate and should not be attributed to the first isolated virus.

The tedious and patient work of the electron microscopist Charles Dauguet is rightly acknowledged in the story accompanying the commentary4. However, the analogy between lymphadenopathy-associated virus (LAV) and the animal lentiviruses became clear only in June 1983, on the suggestion of my virologist colleague, Oswald Edlinger. At that time, Gallo still maintained that an HTLV-like virus was the cause of AIDS, leading to a harsh scientific controversy. Our expanded team was accumulating data indicating that LAV was the cause of AIDS and related syndromes: their tropism for CD4+ T lymphocytes, isolation of the same type of virus from African patients and hemophiliacs, and epidemiological correlation between antibodies against LAV proteins and the disease. Meanwhile, Gallo and his coworkers (in particular Mikulas Popovic) isolated viruses similar to ours, and in early 1984 brought forth more convincing evidence for their causal relationship with AIDS.

I do not wish to minimize the contributions of Barré-Sinoussi, who was the first to recognize the presence of a retrovirus in lymphocyte culture medium by detecting reverse-transcriptase activity and analyzing its physical properties. She deserved to be named first author in the paper I hastily wrote in April 1983 and that was published the following month5. On the other hand, it is important to keep the published scientific record accurate and to acknowledge and recognize all of the authors of our 1983 paper, as well as our collaborators and colleagues who worked with us in the following months and years to investigate this new and deadly disease.

See Reply to “Historical accuracy of HIV isolation” by Françoise Barré-Sinoussi.