AIDS: The Process of Discovery

Letters from: [ Harold Varmus and William Paul ][1] [ Robert Gallo ][1] [ Michael Balter ][1] We were pleased to see recent advances against the human immunodeficiency virus (HIV) proclaimed as Science 's Breakthrough of the Year ([20 Dec., p. 1988][2]). We wish, however, to correct Michael Balter's description of how chemokine receptors came to be recognized as co-receptors for HIV. The pivotal finding, to which Balter's article gives only glancing attention, was the identification of a seven-transmembrane protein—initially called fusin, only later recognized as a receptor (CXCR4) for a chemokine (SDF)—as the HIV co-receptor in T cells (Reports, [10 May, p. 872][3]) ([1][4]). This discovery, which ended a 10-year search by many laboratories for the elusive co-receptors, was based on the use of a screening method that could, in principle, have detected any kind of co-receptor, not just one that happened to be a chemokine receptor. Only after the prepublication announcement and discussion of this result at scientific meetings was it appreciated that HIV co-receptors might be chemokine receptors, thus providing a possible explanation for the inhibition of macrophage-tropic HIV by RANTES and MIP-1 chemokines described some months earlier by F. Cocchi et al . (Reports, [15 Dec. 1995, p. 1811][5]) ([2][6]). With that insight, several laboratories quickly succeeded in showing that CCR-5, the known receptor for these inhibitory chemokines, is the HIV co-receptor in macrophages. 1. 1.[↵][7] 1. Y. Feng, 2. C. C. Broder, 3. P. E. Kennedy, 4. E. A. Berger , Science 272, 872 (1996). [OpenUrl][8][Abstract][9] 2. 2.[↵][10] 1. F. Cocchi 2. et al. , ibid. 270, 1811 (1995). [OpenUrl][11] # {#article-title-2} Balter, in a very nice synopsis of Science' s selection for the most important advances of the year, “New hope in HIV disease,” focuses on the two major advances: (i) development by the pharmaceutical industry of the new inhibitors of HIV (providing better therapy) and (ii) the discovery of the chemokine control of HIV and use of the chemokine receptors by HIV to enter cells (conceptual advance and possible future therapy and vaccine implications). I agree with his comments, but his reference to the chemokine work is partly wrong. Balter states that the chemokine discovery by Cocchi et al. was made at the U.S. National Cancer Institute in Bethesda, Maryland, and at the San Raffaele Scientific Institute in Milan. All the work was conceived and done in my laboratory at the National Cancer Institute. None of it was conceived or carried out at San Raffaele. Subsequently, most of us formed and joined the new Institute of Human Virology (IHV) at the University of Maryland, Baltimore, where the work continues. One of us (P. Lusso) moved to San Raffaele but also enjoys a secondary appointment at the IHV. # Response {#article-title-3} The letters by Varmus and Paul and by Gallo reflect behind-the-scenes competition and conflicts well known to most U.S.-based researchers. I believe that in both cases my description of events does not require correction. [1]: /lookup/doi/10.1126/science.275.5297.140a [2]: /lookup/volpage/275/1988 [3]: /lookup/volpage/275/872 [4]: #ref-1 [5]: /lookup/doi/10.1126/science.275.5307.1811 [6]: #ref-2 [7]: #xref-ref-1-1 "View reference 1. in text" [8]: {openurl}?query=rft.jtitle%253DScience%26rft.stitle%253DScience%26rft.issn%253D0036-8075%26rft.aulast%253DFeng%26rft.auinit1%253DY.%26rft.volume%253D272%26rft.issue%253D5263%26rft.spage%253D872%26rft.epage%253D877%26rft.atitle%253DHIV-1%2BEntry%2BCofactor%253A%2BFunctional%2BcDNA%2BCloning%2Bof%2Ba%2BSeven-Transmembrane%252C%2BG%2BProtein-Coupled%2BReceptor%26rft_id%253Dinfo%253Adoi%252F10.1126%252Fscience.272.5263.872%26rft_id%253Dinfo%253Apmid%252F8629022%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Mzoic2NpIjtzOjU6InJlc2lkIjtzOjEyOiIyNzIvNTI2My84NzIiO3M6NDoiYXRvbSI7czoyNDoiL3NjaS8yNzUvNTI5Ny8xNDAuMi5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30= [10]: #xref-ref-2-1 "View reference 2. in text" [11]: {openurl}?query=rft.jtitle%253Dibid.%26rft.volume%253D270%26rft.spage%253D1811%26rft.atitle%253DIBID%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx