Open Thread, September, 2010-- part 2

NancyLebovitz

This thread is for the discussion of Less Wrong topics that have not appeared in recent posts. If a discussion gets unwieldy, celebrate by turning it into a top-level post.

jacob_cannell:

Take a random sample of perfectly healthy test subjects. Now inject half of them with HIV and half with a placebo, and follow their health over the long term. That is about the only test that could get you 99% accuracy, and it is obviously not ethical.

There have been documented cases of accidental HIV infection of lab workers and dental patients that are not too terribly far from such a controlled experiment. See: S.J. O'Brien and J.J. Goedert, "HIV causes AIDS: Koch's postulates fulfilled," Current Opinion in Immunology, Vol. 8, Issue 5, October 1996, pp. 613-618.

UPDATE: Ungated link to the paper here.

I'm not a skeptic, but I am a bit surprised that three infected lab workers is considered evidence worth mentioning. I'm accustomed to seeing clinical studies with fewer than 100 patients treated as merely suggestive, and several hundred or even thousands of patients necessary to convince regulatory authorities that there is a real phenomenon. So when I read that "three laboratory workers...became infected", it strikes me as anecdotal. Of course you take what you can get, but still, it seems a small group.

My experience is with pharmaceuticals, wh... (read more)

1jacob_cannell16y

Ok, so I have finished reading O'Brien and JJ Goedert. I think the accidental lab worker cases probably have low utility in distinguishing between pathologic HIV and passenger HIV theories, but the animal SIV studies potentially fulfill the ideal experiment design. If animals injected with pure close SIV analogs to HIV develop AIDS-like illness, that is about as good as evidence as one could hope for. For the lab worker infections, they say that the genomes are close to the clonal strain used in the lab, but they don't have a good probalistic model for this: [...] threefold more or less variation doesn't sound like much to me, and regardless even assuming they did all get infected via the lab, it doesn't mention treatment, so we don't know if they were treated with AZT or what. I think the animal models are more interesting - as all the drug cofounding variables are eliminated and everything is controlled. The authors discuss 3 animal models - baboons, some wierd knockout mice with human t-cell graphs, and finally SIV injected into rhesus monkeys. They spend the most time discussing the latter paper so I looked into it. "Induction of AIDS in Rhesus Monkeys by Molecularly Cloned Simian Immunodeficiency". In short, all 5 of the monkeys injected later become seropositive, and 50% of them progress to AIDs-like illnesses and die. Presumably some are naturally resistant. There is a potential issue to this otherwise smoking gun, which is that it appears they had to inject whole culture of T-cells, as the virus can not be isolated directly into plasmid vectors: [...] But if all they had then was provirus integrated into PBL ( peripheral blood lymphocytes ), then one must wonder about the risk of graft versus host disease, and transfusion reaction in general. Basically, the foreign T-cell line can actively invade and cause all kinds of havoc. Perhaps they have controlled for that and I'm completely off, but I don't see where they mention it. OBrien and Goodart con

4RobinZ16y

The article (listed as a "guest editorial", I note for completeness) has the following citations in the relevant section: 52. Weiss SH, Goedert JJ, Gartner S, Popovic M, Waters D, Markham P, Veronese FD, Gall MH, Barkley WE, Gibbons J et al.: Risk of human immunodeflciency virus (HIV-1) infection among laboratory workers. Science 1988, 239:68-71. 53. Reitz MS Jr, Hall L, Robert-Guroff M, Lautenberger J, Hahn BH, Shaw GM, Kong LI, Weiss SH, Waters D, Gallo RC, Blattner W: Viral variability and serum antibody response in a laboratory worker infected with HIV-1 (HTLV-IIIB). AIDS Res Hum Retroviruses 1994, 10:1143-1155. 54. Guo HG, Waters D, Hall L, Louie A, Popovic M, Blattner W, Streicher H, Gallo RC, Chermann JC, Reitz MS: Nucleotide sequence analysis of the original isolate of HIV-1. Nature 1991, 349:745-746. 55. Wain-Hobson S, Vartanian JP, Henry M, Chenciner N, Cheynier R, Delassus S, Martins LP, Sala M, Nugeyre MT, Guetard D et al.: LAV revisited: origins of the early HIV-t isolates from Institut Pasteur. Science 1991, 252:961-965. 56. Wolinsky SM, Wike CM, Korber BTM, Hutto C, Parks WP, Rosenblum LL, Kunstman KJ, Furtado MR, Munoz JL: Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science 1992, 255:1134-1137. 57. Morbidity Mortality Weekly Report of the Center for Disease Control: Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults (1993). 1992:1-19.