Holy Grails, Unicorns, and HIV Vaccines

The three subjects of my title have these things in common:

1. No one can produce an authentic specimen.
2. All the evidence for their existence is anecdotal and based on human testimony.
3. Dedicated and ingenious quests have failed to locate an authentic specimen.
4. Nevertheless, their existence is attested by a cult of true believers.

These commonalities occurred to me as I was rummaging in my old files and became rather surprised at the number of mentions of HIV vaccines: new clues for what could lead to a vaccine; promising breakthroughs in understanding how to construct a vaccine; grants from private and public agencies for research on vaccines; organizations set up to facilitate cooperative work toward a vaccine; clinical trials of potential vaccines — and failure after failure after failure. Here is just a small sample from my randomly gathered files:

1984: Vaccine probably within a couple of years
—— Robert Gallo: “Oh, possibly in a couple of years”, cited at p. 176 in Great Feuds in Medicine by Hal Hellman (Wiley, 2002);
—— Margaret Heckler, 23 April press conference: “We hope to have such a vaccine ready for testing in about two years”, cited at p. 25 in The AIDS Bureaucracy by Sandra Panem (Harvard University Press, 1988); at p. 64 in AIDS at 30: A History by Victoria A. Harden (Potomac Books, 2012).

1985: “Recent demonstrations of neutralizing antibodies in AIDS and pre-AIDS patients . . . are encouraging for the prospects of a vaccine”
—— Wong-Staal & Gallo, “Human T-lymphotropic retroviruses”, Nature, 317 (1985) 395-403.

But 10 years later, no success and not even any obvious advance:
1995: However, “Nobody can say the data were encouraging. It’s all smoke and mirrors. There’s nothing there”, according to AIDS vaccine researcher John P. Moore
—— Jon Cohen, Shots in the Dark: The Wayward Search for an AIDS Vaccine (Norton, 2001), p. 275.

1999: Elite controllers of HIV could lead to vaccine development
—— Sarah Rowland-Jones, “Long-term non-progression in HIV infection: Clinico pathological issues”, Journal of Infection, 38 (1999) 67-70.
—— Philippa J. Easterbrook, “Long-term non-progression in HIV infection: definitions and epidemiological issues”, Journal of Infection, 38 (1999) 71-3.

1999: “Promising results for Vical’s HIV vaccine”
—— New Statesman, 30 November 1999.
By 2007, not so promising: “NIH determined that it would not conduct the PAVE 100 study”.
—— Vical, “HIV Vaccine”.

2005: “[D]evelopment of an HIV vaccine remains one of the most difficult challenges confronting biomedical research today”
—— Coordinating Committee of the Global HIV/AIDS Vaccine Enterprise, “The Global HIV/AIDS Vaccine Enterprise: Scientific Strategic Plan”, PLoS Medicine, 2 #2 (2005) e25, pp. 0111-0121.

2006: “[A]bout 2,000 . . . controllers worldwide whose entire genetic makeups will be carefully examined by an international team of scientists as part of the quest to discover an AIDS vaccine”
—— Warren King, “Rod Fichter has lived with HIV for 20 years with no symptoms”, Seattle Times, 23 November 2006.

2006: “As many as one in 300 HIV patients never get sick . . . . their cases can help in the search for a vaccine”
—— Maggie Fox, “ ‘Elite’ HIV patients mystify doctors”, Reuters, 16 August 2006;

2006: Elite controllers of HIV could lead to vaccine development (cf. 1999).
—— Marmor et al., “Resistance to HIV Infection”, J. Urban Health, 83 (2006) 5-17.

2006: “Swedish prime-boost HIV DNA vaccine shows strong responses”
—— Keith Alcorn, 1 September 2006; http://www.aidsmap.com/en/news/2BA54617-51CC-4DBF-BE75-FCD85359592E.asp?type=preview, accessed 23 September 2006 (broken link).

2006: “Is an AIDS vaccine possible? Experts more optimistic after annual vaccine meeting”
—— Keith Alcorn, 5 September 2006; http://www.aidsmap.com/en/news/4AF3F36A-6A14-4C0A-BB4F-1ADE008F80E7.asp?type=preview, accessed 23 September 2006 (broken link).

2007: “[W]ill help with the design of an HIV vaccine”
—— “Novel genetics research advances possibility of HIV vaccine”, ScienceDaily.com, 8 July 2007; .

2007: Elite controllers of HIV could lead to vaccine development (cf. 1999)
—— O. J. Fagbire, “Elite controllers of HIV could lead to vaccine development”, 10 June 2007; http://www.vaccinerx.com/news/latest/elite-controllers-of-hiv-could-lead-to-vaccine-development-20070610-332-26.html, accessed 21 June 2007 (broken link).

2007: But immune response to one strain of “HIV” may not protect against other strains
—— Piantadosi et al., “Chronic HIV-1 infection frequently fails to protect against superinfection”, PLoS Pathog, 3 (2007) e177.

2007: “Ending of HIV vaccine trial jolts industry. . . . Merck had assembled the latest thinking on a 20-year quest . . . . had spent more than a decade devising the best ways . . . . the vaccine did not seem to be working. More people among the vaccinated group were getting the virus than those receiving a placebo. . . . roughly 90 percent of vaccine studies were using major elements of Merck’s approach. . . . John W. Shiver, who heads Merck’s basic research in vaccines . . . [and] is credited with several research advances, said he did not think any current approach would work. . . . a new burst of creativity was needed” [emphasis added].
—— Karl Stark, “Ending of HIV vaccine trial jolts industry Merck’s case was a failure of a product, not a failure of the vaccine’s concept”, philly.com, 7 October 2007.

2007: “[D]ata from . . . a 52 weeks clinical trial . . . did not show a clear advantage of . . . second generation HIV vaccine, IR103, over its original whole-killed HIV vaccine, REMUNE(R)”
—— “Orchestra Therapeutics discontinues its HIV vaccine development program”, PRNewswire-FirstCall, 17 July 2007; http://money.cnn.com/news/newsfeeds/articles/prnewswire/LATU16717072007-1.htm, accessed 18 July 2007 (broken link).

2007: “Scientists unveil piece of HIV protein that may be key to AIDS vaccine development”
—— NIH News, 14 February 2007; .

2007: “Novavax and collaborators significantly improve VLP vaccine for HIV/AIDS: Plans under way to advance new vaccine into clinical testing”
—— PRNewswire, 16 January 2007.

2008: “[T]he protein, FOX03a, shields against viral attacks and . . . the discovery will help in the development of a HIV vaccine”
—— “HIV breakthrough: Protein that fights immunodeficiency identified”, ScienceDaily.com, 3 March 2008.

2008: “HIV isolate from Kenya provides clues for vaccine design”
—— EurekAlert, 2 January 2008
—— Blish et al., “Enhancing exposure of HIV-1 neutralization epitopes through mutations in gp41”, PLoS Med., 5 (#1, 2008) e9.

2008: Review: “Immune correlates of protection against HIV-1 infection”
—— Piacentini et al., “Not just sheer luck! Immune correlates of protection against HIV-1 infection”, Vaccine, 26 (2008) 3002-7.

2008: “Scientists are no further forward in developing a vaccine against HIV after more than 20 years of research, a Nobel Prize-winning biologist [David Baltimore] has said”
—— Helen Briggs, “HIV vaccine research hits impasse”, BBC News, 15 February 2008.

2008: “Despite hundreds and hundreds of millions of dollars, the reality in 2008 is that an HIV vaccine clearly remains beyond our grasp” [emphasis added]
—— Warner Greene, cochair of the HIV Vaccine Summit, cited in Bob Roehr, “NIH to Refocus HIV Vaccine Research”, 3April 2008; http://www.pridesource.com/article.shtml?article=29862, accessed 10 April 2008 (broken link).

2008: “Critics fear worst for new SA HIV vaccine”
—— Bobby Jordan, Sunday Times (South Africa), 13 April 2008.

2008: “Most scientists involved in Aids research believe that a vaccine against HIV is further away than ever and some have admitted that effective immunisation against the virus may never be possible, according to an unprecedented poll conducted by The Independent” [emphasis added]
—— Steve Connor & Chris Green, “Is it time to give up the search for an Aids vaccine? After 25 years and billions of pounds, leading scientists are now forced to ask this question”, Independent.co.uk, 24 April 2008; .

2012: “[N]ew and promising pathways …promising developments in HIV-1 vaccine design”
—— Kwong et al., “The changing face of HIV vaccine research”, J Int AIDS Soc., 15 (2012) 17407.

2013: “[A] major setback . . . volunteers who received the vaccination shot were more likely to contract the virus than those who were given a placebo. . . . Dr. Anthony Fauci called the results of the trial a ‘disappointment’ but added that the study yielded ‘important information’ that would help guide future research”
—— Katie McDonough, “Failed HIV vaccine clinical trial shut down — Researchers faced a major setback in the pursuit of an HIV vaccine after the shot was shown to be ineffective”, Salon.com, 26 April 2013; .

*   *   *   *   *   *   *   *

With the Holy Grail and with unicorns, the intellectual mainstream of modern Western society has concluded that the anecdotal human testimony can be explained in other ways than the actual existence of the purported items. For various reasons, that conclusion has not yet been reached by a societal consensus on the matter of HIV vaccines. For one thing, HIV vaccines are taken to be matters of “science”, and society doesn’t disagree with whatever the mainstream consensus happens to be at any given time in any given scientific specialty. AIDS Rethinkers and HIV Skeptics, on the other hand, have very good explanations for the persistent failure of attempts to construct an HIV vaccine: HIV doesn’t exist.

How could I describe the evidence as “anecdotal and based on human testimony”? Simply because authentic virions of HIV have never been isolated direct from an “HIV-positive” individual. All research is based on so-called “isolates” of HIV, which are mixtures of many substances that originate in a particular density layer of solutions taken from cultures in which various active ingredients were mixed with material extracted from supposedly infected people. There is no gold-standard HIV test for this very reason; authentic naturally occurring HIV virions have never been demonstrated to exist. Yet vaccines are intended to work again such virions and their subsequent actions.

The mainstream HIV/AIDS literature is replete with the most intricate technical details and the most ingenious speculative attempts to explain results that should not be obtained if HIV/AIDS theory were correct. Yet every failure of HIV/AIDS theory just stimulates upholders of the faith to ever more arcane researches. One is reminded of the classic description of the sociology of cognitive dissonance: When the predicted Day of Judgment did not arrive on the calculated date, the underlying theory (=faith) was not questioned let alone abandoned; instead, new calculations delivered a new date — When Prophecy Fails: A Social and Psychological Study of A Modern Group that Predicted the Destruction of the World (Leon Festinger, Henry Riecken, & Stanley Schachter, Harper, 1956).

I acknowledged that my list of items is just a small sampling. PubMed is the abstracting and indexing service of the National Library of Medicine, National Center for Biotechnology Information, National Institutes of Health. A PubMed search for “HIV vaccine” yielded 15,000 results and for “AIDS vaccine” 10,000 results. There may be some duplication, but the number of technical articles published in the medical-scientific literature about vaccines against “HIV/AIDS” is at the very least 15,000 and may be in excess of 25,000; moreover, the vast majority of those will have described promising paths toward a vaccine, because disappointing results hardly ever get published.
Google Scholar returns 838,000 results for “HIV vaccine” and 510,000 for “AIDS vaccine”, indicating that interest beyond the strictly technical is high among academics, for example speculating about behavioral, economic, sociological aspects of a potential vaccine
The popular media amplify all these professional writings: A Google search for “HIV vaccine” yielded 20 million hits and 19 million for “AIDS vaccine”.

That’s a lot of words about something that may well be a mirage.

For lay people, the best way to think about the search for an HIV vaccine (or “AIDS vaccine”) is to recognize it as belonging to the genre of quests for the Holy Grail or for unicorns.

Gallo’s failed application for a Nobel Prize

Reading some stuff from the early days of AIDS, I came across the “Review Article” by Wong-Staal and Gallo, “Human T-lymphotropic retroviruses” (Nature, 317 [1985] 395-403).

The piece qualifies for scare quotes around Review Article because it’s actually just blatant self-promotion by way of assertions that are, to say the very least, dubious.
Thus Gallo is credited (credits himself) with discovering the “first human retroviruses”, HTLV-I and HTLV-II which are asserted causes of adult-onset leukemia (ATL), in which T-cells proliferate cancerously.
He is also credited with the discovery of HTLV-III, which was later re-named HIV as a compromise after it had been established conclusively to have been a clone of Montagnier’s LAV. Perhaps to discount further Montagnier’s claim to priority, “Subsequent studies demonstrated that . . . [HTLV-I and HTLV-II] were closely related to the LAV isolate”.
Gallo’s claim to priority is also stated quite explicitly: “The idea and the approach to the identification of a unique human T-lymphotropic retrovirus in AIDS is largely derived from epidemiological data and from studies on HTLV-I. The idea was first proposed by R.C.G., based on several considerations derived in part from discussion with M. Essex”.

HTLV-III is asserted to be kin to HTLV-I and HTLV-II because they all affect T-cells, even though III does the opposite from what I and II do: it kills cells rather than causing their proliferation. To further underscore that they are all in the same family of (Gallo-discovered) human retroviruses, we are told that “the term HTLV-III does not depend on an arbitrary extent of nucleotide sequence homology to HTLV-I and HTLV-II” — in other words, biological kinship is not decided on the basis of genetics!? When it is genetics that determines kinship in all other realms of biology? And in what way was LAV then “closely related” to the HTLVs?

On the other hand, it is asserted that “Molecular clones of the genomes of all three subgroups of HTLV have been obtained [references 82-88] and the complete nucleotide sequence of one or more isolates of each subgroup has been published [references 89-95]”.
It’s a nice trick, it seems to me, to get the compete genomes of entities that have never been isolated in pure form. How do you molecularly clone something that is not a pure substance?
But then Gallo asserted as late as 2006, in his testimony in the Parenzee trial in Australia, that because he could make a lot of virus therefore purification was not needed:
“Once we could mass-produce this virus, that’s purification. If you have a tonne of something and you contaminate it by a drop of water, didn’t you purify it? . . . . virus comes out in great quantity and forever, thus making purification already accomplished” (p. 1278); “mass-produced virus . . . by itself is purified virus” (p. 1281 of Parenzee trial transcript).

Gallo’s idiosyncratic attitude toward purification seems even more remarkable given that his “review” mentions “the heterogeneity of different HTLV-III isolates”. Of course they’re heterogeneous, since they contain all sorts of stuff because the purported “HTLV-III” was never separated from the other material. Biologists should surely be as aware as are other scientists of the possible effects that even the tiniest contamination might exert, since those contaminants might be catalytic (or enzymatic) in their action — see “Purify? Who needs that? (So says Robert Gallo)”.

Assertions of which I was previously unaware include that “the leukemia virus (HTLV-I) can also cause immunosuppression and opportunistic infections, and it is possible that the immunosuppressive virus (HTLV-III or lymphadenopathy-associated virus, LAV) can cause leukemia once its cytopathic property is blocked”. “HTLV-I and HTLV-II also showed immune suppressive activity in vitro and . . . [there were] opportunistic infections in ATL patients”; “properties of HTLV-I are limited manifestations of the more profound immunosuppressive and cytopathic properties of HTLV-III”. In a similar vein, in his autobiography Gallo asserts that HTLVs I and II are “the only known specific co-factors for AIDS” (emphasis in original, p.
248 in Gallo’s autobiographical Virus Hunting: AIDS, Cancer, and the Human Retrovirus: A Story of Scientific Discovery, Basic Books, 1991).

Another assertion of similarity is that all three HTLVs have similar modes of transmission: “sexual, congenital and blood”. It seems odd to lump congenital transmission, which surely means hereditary, endogenous, with the other two, which function via exogenous infective agents. Gallo continued to make this puzzling assertion for many years; it appears also in his autobiography (p. 114 in Virus Hunting): “HTLV-I, ‘tended to be transmitted within families and to stay within families for generations’”.

I found it interesting to read that antigens of HTLV-I cross-react with those of “the AIDS agent”, in other words that “HIV” tests were known from the very beginning to be not specific to HIV. Also interesting was the assertion that HTLV-III “is only indirectly involved in . . . Kaposi’s sarcoma . . . as viral genetic information is . . . not detectable in Kaposi tunor . . . . [which] can occur in the absence of any apparent T-cell defect”: So it was also known from the very beginning that Kaposi’s sarcoma, originally iconic of “AIDS”, had nothing to do with immune deficiency or presence of HIV.

The assertion of observed cell-killing in vitro by HTLV-III was contradicted later in Montagnier’s lab, where it was found that the cell-killing agent could be inactivated by antibiotic and was therefore probably a mycoplasma and not a virus: Lemaître et al., “Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells”, Research in Virology, 141 (1990) 5-16; “Role of mycoplasma infection in the cytopathic effect induced by human immunodeficiency virus type 1 in infected cell lines”, Infection and Immunity, 60 (1992) 742-8.

I noted that with “HTLV-III, infection is followed by persistence of unintegrated . . . DNA”, recalling that Etienne de Harven has pointed out that such random circulating DNA could give rise to positive “HIV” tests — “Human Endogenous Retroviruses and AIDS Research: Confusion, Consensus, or Science?”, Journal of American Physicians and Surgeons, 15 (#3, 2010) 69-74, .

And this “Review” repeats the optimistic view expressed in the notorious press conference of April 1984: “Recent demonstrations of neutralizing antibodies in AIDS and pre-AIDS patients . . . are encouraging for the prospects of a vaccine” — prospects that remain nothing beyond prospects even some 3 decades later.

This not-so-subtle attempt to come to the attention of the Nobel Committee culminates in Table 1, where similarities between HTLVs I and II and III are listed, together with asterisked items supposed to be unique to Gallo’s HTLVs, including that they are human, exogenous, infectious retroviruses; show particular T4 tropism; that there are highly related viruses (STLV-I, STLV-III) in Old World monkeys; as well as some technical aspects of the genome.

That this article appeared in Nature says things not only about that journal’s claim to pre-eminence but also about the nature of peer review and its purported role in safeguarding the quality of the scientific literature. Much of what I criticize here required no later knowledge to understand its flaws. For a fully documented analysis of the misdeeds of Gallo’s laboratory, see John Crewdson’s Science Fictions: A Scientific Mystery, a Massive Cover-Up, and the Dark Legacy of Robert Gallo (Little, Brown, 2002). Gallo was spared the ignominy of a finding of scientific misconduct only by administrative intervention: “HHS: Gallo Guilty of Misconduct “Federal inquiry finds misconduct by a discoverer of the AIDS Virus” (Science, 259 [1993] 168-70); “Excerpts from conclusions of report of the Office of Research”;  “Report found scientific misconduct”.