OPV AIDS hypothesis
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The oral polio vaccine (OPV) AIDS hypothesis suggests that the AIDS pandemic originated from live polio vaccines prepared in rhesus macaque tissue cultures and then administered to up to one million Africans between 1957 and 1960 in experimental mass vaccination campaigns.
Data analyses in molecular biology and phylogenetic studies contradict the OPV AIDS hypothesis; consequently, scientific consensus regards the hypothesis as disproven. The journal Nature has described the hypothesis as "refuted".
Background: polio vaccines
Two vaccines are used throughout the world to combat poliomyelitis. The first polio vaccine, developed by Jonas Salk, is an inactivated poliovirus vaccine (IPV), consisting of a mixture of three wild, virulent strains of poliovirus, grown in a type of monkey kidney tissue culture (Vero cell line), and made noninfectious by formalin treatment. The second vaccine, an oral polio vaccine (OPV), is a live-attenuated vaccine, produced by the passage of the virus through non-human cells at a sub-physiological temperature. The passage of virus produces mutations within the viral genome, and hinders the virus's ability to infect nervous tissue.
Both vaccines have been used for decades to induce immunity to polio, and to stop the spread of the infection. However, OPV has several advantages; because the vaccine is introduced in the gastrointestinal tract, the primary site of poliovirus infection and replication, it closely mimics a natural infection. OPV also provides long lasting immunity, and stimulates the production of polio neutralizing antibodies in the pharynx and gut. Hence, OPV not only prevents paralytic poliomyelitis, but also, when given in sufficient doses, can stop a threatening epidemic. Other benefits of OPV include ease of administration, low cost and suitability for mass vaccination campaigns.
Oral polio vaccine
Oral polio vaccines were developed in the late 1950s by several groups, including those led by Albert Sabin, Hilary Koprowski and H. R. Cox. A poliovirus type 1 strain called SM was reported in 1954. A less virulent version of the SM strain was reported by Koprowski in 1957. The name of the vaccine strain was "CHAT" after "Charlton", the name of the child who was the donor of the precursor virus. The Sabin, Koprowski and Cox vaccines "were clinically tested in millions of individuals and found to be safe and effective". Because monkey trials found fewer side effects with the Sabin vaccine, in the early 1960s, the Sabin vaccine was licensed in the USA and its use supported by the World Health Organization.
Between 1957 and 1960, Koprowski's vaccine was administered to roughly one million people in the Belgian territories, now the Democratic Republic of the Congo, Rwanda and Burundi. In 1960, Koprowski wrote in the British Medical Journal, "The Belgian Congo trials have enlarged considerably and ... more vaccination campaigns organized in several provinces of the Belgian Congo are raising the number of vaccinated individuals into the millions."(p. 90) Koprowski and his group also published a series of detailed reports on the vaccination of 76,000 children under the age of 5 (and European adults) in the area of Leopoldville (now Kinshasa) in Belgian Congo from 1958–1960; these reports begin with an overview, next a review of safety and efficacy, then a 21-month follow-up and final report.
In the 1950s, before dangers inherent to the process were well controlled, seed stocks of vaccines were occasionally transported to distant regions, then standard tissue culture methods were used to amplify the virus at local production facilities. Biologic products, chiefly kidney cells for cultures and blood serum for media, were sometimes harvested from local primates and used in the production process if wild or captive populations of appropriate species were available. In South Africa, African green monkey tissue was used to amplify the Sabin vaccine. In French West Africa and Equatorial Africa, baboons were used to amplify a vaccine from the Pasteur Institute. In Poland, the CHAT vaccine was amplified using Asian macaques.
Development of hypothesis
In 1987, Blaine Elswood contacted journalist Tom Curtis about a "bombshell story" on OPV and AIDS. Curtis published an article on the OPV AIDS hypothesis in Rolling Stone in 1992. In response, Hilary Koprowski sued Rolling Stone and Tom Curtis for defamation. The magazine published a clarification which praised Koprowski and stated:
The editors of Rolling Stone wish to clarify that they never intended to suggest in the article that there is any scientific proof, nor do they know of any scientific proof, that Dr. Koprowski, an illustrious scientist, was in fact responsible for introducing AIDS to the human population or that he is the father of AIDS.
A few scientists, notably the biologist W.D. Hamilton, thought the hypothesis required serious investigation, but they received little support from the scientific community.
Journalist Edward Hooper detailed the hypothesis in his 1999 book, The River. Hooper further expanded on his allegations in a 2000 meeting in London, at the Royal Society, although these claims were later rebutted by some of the scientists who were present at the meeting. In 2001, Hilary Koprowski responded by making a detailed rebuttal of the points made in the book, also in a talk to the Royal Society. In 2004, the Origin of Aids, a French TV documentary strongly supportive of the OPV hypothesis, appeared on several television stations around the world.
In 2003, Edward Hooper published additional statements that he believed supported his hypothesis in an article in the London Review of Books. These included accounts of in interview with Jacques Kanyama, a virology technician at the lab in Stanleyville (the Laboratoire Médical de Stanleyville (LMS)) responsible for testing the CHAT vaccine and performing the initial set of vaccinations, who was reported to have said that batches of CHAT had been produced on site by Paul Osterrieth. In addition, Philip Elebe, a microbiology technician, was claimed to have said that tissue cultures were being produced from Lindi chimpanzees. Osterrieth has denied these claims and stated that this work would not have been possible in this laboratory, stating that:
at no time did I ever attempt to make cell cultures from chimpanzee tissues. In addition, I wish to state categorically that no poliovaccine was ever produced or could have been produced in Stanleyville, since the facilities were totally inadequate for the production or control of poliovaccine.
In his book, Hooper also stated that Gaston Ninane was involved in using chimpanzee cells to produce vaccine in Congo. Ninane responded to this allegation by stating that he could "categorically deny" ever having tried to make tissue cultures from chimpanzee cells. The people involved in vaccine production and distribution from America state that no vaccine was prepared locally in Congo and that only the CHAT vaccine from America was used. Barbara Cohen, the technician who was responsible for running the American laboratory that produced this vaccine stated:
At no time did I ever receive or work on chimpanzee kidneys, nor to my knowledge cells derived from chimpanzees. I never made, nor do I know of anyone in the lab who made polio vaccine in chimpanzee cells.
The OPV AIDS hypothesis has been examined and criticized by members of the scientific and medical communities as being unsupported or directly contradicted by available data, and inconsistent with HIV epidemiology.
In an August 1992 letter published in Science, Koprowski repudiated the OPV AIDS hypothesis, pointing to multiple errors of fact in its assertions. In October 1992, Science ran a story titled "Panel Nixes Congo Vaccine as AIDS source," describing the findings of an independent panel which found each proposed step in the OPV-AIDS hypothesis "problematic". The story concluded:
...it can be stated with almost complete certainty that the large polio vaccine trial... was not the origin of AIDS.
The oldest confirmed sample of human tissue that shows the presence of HIV-1 is an archival sample of plasma collected from an anonymous donor in the city of Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo) in 1959. Initial phylogenetic analyses, published in 1999, led the researchers to hypothesise that HIV-1 entered "into the African population not long before 1959."
In 2000, the Royal Society held a meeting to discuss data on the origin of AIDS; the OPV AIDS hypothesis was a central topic of discussion. At this meeting, three independent labs released the results of tests on the remaining stocks of Koprowski's vaccine, which Edward Hooper had demanded in The River. The tests confirmed Koprowski's contention that his vaccine was made from monkey, rather than chimpanzee, kidney, and found no evidence of SIV or HIV contamination. Additional epidemiologic and phylogenetic data was presented at the conference which undermined other aspects of the OPV AIDS hypothesis. According to a report in Science, Hooper "did not challenge the results; he simply dismissed them." Brian Martin, a proponent of the OPV AIDS hypothesis, argued at the conclusion of the conference that if other AIDS-origin hypotheses were scrutinized in such detail, they would prove equally unsatisfying.
In 2001, three articles published in Nature examined various aspects of the OPV-AIDS hypothesis, as did an article published in Science. In every case, the studies' findings argued strongly against any link between the polio vaccine and AIDS. The evidence cited included multiple independent studies that dated the introduction of HIV-1 to humans as occurring between 1915 and 1941, probably in the 1930s. These results were confirmed by a later study using samples from the 1960s that also found that the epidemic began between 1908 and 1930, and a study that showed that although recombination amongst viruses makes dating less precise, it does not significantly bias estimates in either direction (it does not introduce a systematic error).
The author of one of the studies, evolutionary biologist Edward Holmes of Oxford University, commented in light of the new evidence: "Hooper's evidence was always flimsy, and now it's untenable. It's time to move on." An accompanying editorial in Nature concluded:
The new data may not convince the hardened conspiracy theorist who thinks that contamination of OPV by chimpanzee virus was subsequently and deliberately covered up. But those of us who were formerly willing to give some credence to the OPV hypothesis will now consider that the matter has been laid to rest.
The possibility that chimpanzees found near Kisangani in the Democratic Republic of Congo (formerly Stanleyville) were, indirectly, the true source of HIV-1 was directly addressed in a 2004 study published in Nature. Here, the authors found that while SIV was present in chimpanzees in the area, the strain of SIV infecting these chimpanzees was phylogenetically distinct from all strains of HIV, providing direct evidence that these particular chimps were not the source of HIV in humans.
Edward Hooper responded to these studies by either denying their relevance to the OPV hypothesis, disputing their accuracy, or asserting the existence of a "large organised cover-up".
Current oral polio-vaccine campaign in Africa
Rumours that polio vaccines are unsafe disrupted the longstanding effort of the WHO and UN to achieve poliomyelitis eradication worldwide through use of the oral polio vaccine of Albert Sabin, which is thought to be safe and effective by virtually all medical authorities. If this long-term public-health goal could be achieved, poliomyelitis would follow smallpox as the second eradicated infectious human disease. The OPV AIDS hypothesis relates only to the historical origin of AIDS, and its proponents have accepted the safety of the modern polio vaccines, but rumors based on a misunderstanding of the hypothesis exist, and those rumors are blamed in part for the recent failure to eliminate polio in Nigeria.
By 2003, cases of poliomyelitis had been reduced to just a small number in isolated regions of West Africa, with sporadic cases elsewhere. However, the disease has since resurged in Nigeria and in several other nations of Africa, which epidemiologists trace to refusals by certain local populations to allow their children to be administered the Sabin oral vaccine. The expressed concerns of local populations often relate to fears that the vaccine might induce sterility, and it seems that debate over the OPV-AIDS hypothesis has fueled additional fears. Since 2003, these fears have spread among some in the Muslim community, with Datti Ahmed, of the Supreme Council for Sharia in Nigeria stating that:
“We believe that modern-day Hitlers have deliberately adulterated the oral polio vaccines with anti-fertility drugs and viruses which are known to cause HIV and AIDS.”
- AIDS origins opposed to scientific consensus
- AIDS origin
- SV40 A scientifically accepted case of a monkey virus contaminating polio vaccine – Inactivated poliovirus vaccine (IPV) only.
- Courtois G, Flack A, Jervis GA, Koprowski H, Ninane G (July 1958). "Preliminary report on mass vaccination of man with live attenuated poliomyelitis virus in the Belgian Congo and Ruanda-Urundi". Br Med J 2 (5090): 187–190. doi:10.1136/bmj.2.5090.187. PMC 2026116. PMID 13560820.
- LeBrun A, Cerf J, Gelfand HM, Courtois G, Plotkin SA, Koprowski H (1960). "Vaccination with the CHAT strain of type 1 attenuated poliomyelities virus in Leopoldville, Belgian Congo 1. Description of the city, its history of poliomyelitis, and the plan of the vaccination campaign" (PDF). Bull World Health Organ. 22 (3–4): 203–13.
- Hillis DM (2000). "AIDS. Origins of HIV". Science 288 (5472): 1757–1759. doi:10.1126/science.288.5472.1757. PMID 10877695.
- Birmingham K (2000). "Results make a monkey of OPV-AIDS theory". Nat Med 6 (10): 1067–1067. doi:10.1038/80356. PMID 11017114.
- Cohen J (2001). "AIDS origins. Disputed AIDS theory dies its final death". Science 292 (5517): 615a–615. doi:10.1126/science.292.5517.615a. PMID 11330303.
- Origin of Human Immunodeficiency Virus (HIV/AIDS) Centers for Disease Control and Prevention website , Accessed 30 January 2007
- Worobey M, Santiago M, Keele B, Ndjango J, Joy J, Labama B, Dhed'A B, Rambaut A, Sharp P, Shaw G, Hahn B (2004). "Origin of AIDS: contaminated polio vaccine theory refuted". Nature 428 (6985): 820–820. doi:10.1038/428820a. PMID 15103367.
- Kew O, Sutter R, de Gourville E, Dowdle W, Pallansch M (2005). "Vaccine-derived polioviruses and the endgame strategy for global polio eradication". Annu Rev Microbiol 59 (1): 587–635. doi:10.1146/annurev.micro.58.030603.123625. PMID 16153180.
- Pearce J (2004). "Salk and Sabin: poliomyelitis immunisation". J Neurol Neurosurg Psychiatry 75 (11): 1552–1552. doi:10.1136/jnnp.2003.028530. PMC 1738787. PMID 15489385.
- Furesz J (2006). "Developments in the production and quality control of poliovirus vaccines – Historical perspectives". Biologicals 34 (2): 87–90. doi:10.1016/j.biologicals.2006.02.008. PMID 16621594.
- Plotkin SA; Modlin, J. F.; Plotkin, S. A. (2001). "CHAT oral polio vaccine was not the source of human immunodeficiency virus type 1 group M for humans". Clin. Infect. Dis. 32 (7): 1068–1084. doi:10.1086/319612. PMID 11264036.
- Koprowski H (July 1960). "Historical aspects of the development of live virus vaccine in poliomyelitis". Br Med J 2 (5192): 85–91. doi:10.1136/bmj.2.5192.85. PMC 2096806. PMID 14410975.
- Plotkin SA, LeBrun A, Koprowski H (1960). "Vaccination with the CHAT strain of type 1 attenuated poliomyelitis virus in Leopoldville. Belgian Congo 2. Studies of the safety and efficacy of vaccination" (PDF). Bull World Health Organ 22 (3–4): 215–34.
- Plotkin SA, LeBrun A, Courtois G, Koprowski H (1961). "Vaccination with the CHAT strain of type 1 attenuated poliomyelitis virus in Leopoldville, Congo 3. Safety and efficacy during the first 21 months of study" (PDF). Bull World Health Organ 24 (6): 785–92. PMC 2555526. PMID 13736381.
- Enders, John (1955). "The present status of tissue-culture techniques in the study of poliomyelitis viruses" (PDF). In Debré, R. Poliomyelitis. Geneva: World Health Organization. pp. 269–94.
- Rappaport, Catherine (1956). "Trypsinization of Monkey-Kidney Tissue: Automatic Method for the Preparation of Cell Suspensions" (PDF). Bull World Health Organ 14 (1): 147–66. PMC 2538109. PMID 13329843.
- Melnick, JL (1956) "Tissue culture methods for the cultivation of poliomyelitis and other viruses", in American Public Health Association, Diagnostic Procedures for Virus and Rickettsial Diseases 2nd ed., New York, pp. 97–151
- Rhodes AJ, Wood W, Duncan D (1955). "The present place of virus laboratory tests in the diagnosis of poliomyelitis, with special reference to tissue-culture techniques" (PDF). In Debré, R. Poliomyelitis. Geneva: World Health Organization.237–67
- Plotkin SA (2001). "Untruths and consequences: the false hypothesis linking CHAT type 1 polio vaccination to the origin of human immunodeficiency virus". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356 (1410): 815–823. doi:10.1098/rstb.2001.0861. PMC 1088471. PMID 11405925.
- Curtis, Tom (19 March 1992). "The Origin of AIDS: A startling new theory attempts to answer the question, 'Was it an act of God or an act of man?" (626). Rolling Stone. pp. 54–9, 61, 106, 108.
- Martin B (August 2003). "Investigating the origin of AIDS: some ethical dimensions". J Med Ethics 29 (4): 253–256. doi:10.1136/jme.29.4.253. PMC 1733782. PMID 12930866.
- Plotkin SA, Teuwen DE, Prinzie A, Desmyter J (2001). "Postscript relating to new allegations made by Edward Hooper at The Royal Society Discussion Meeting on 11 September 2000". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356 (1410): 825–829. doi:10.1098/rstb.2001.0875. PMC 1088472. PMID 11405926.
- Koprowski H (2001). "Hypotheses and facts". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356 (1410): 831–833. doi:10.1098/rstb.2001.0869. PMC 1088473. PMID 11405927.
- Aids and the Polio Vaccine Edward Hooper London review of Books 3 April 2003
- Osterrieth PM (June 2001). "Vaccine could not have been prepared in Stanleyville". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356 (1410): 839–839. doi:10.1098/rstb.2001.0872. PMC 1088475. PMID 11405929.
- Osterrieth P (May 2004). "Oral polio vaccine: fact versus fiction". Vaccine 22 (15–16): 1831–1835. doi:10.1016/j.vaccine.2004.01.028. PMID 15121291.
- Koprowski (1992). "AIDS and the Polio Vaccine". Science 257 (5073): 1024–1027. doi:10.1126/science.257.5073.1024. PMID 1509249.
- "Panel nixes Congo trials as AIDS source". Science 258 (5083): 738–9. 1992. doi:10.1126/science.258.5083.738-d. PMID 1439779.
- Zhu T, Korber BT, Nahmias AJ, Hooper E, Sharp PM, Ho DD (1999). "An African HIV-1 sequence from 1959 and implications for the origin of the epidemic". Nature 391 (6667): 594–597. doi:10.1038/35400. PMID 9468138.
- Cohen J (2000). "Forensic epidemiology. Vaccine theory of AIDS origins disputed at Royal Society". Science 289 (5486): 1850–1851. doi:10.1126/science.289.5486.1850. PMID 11012346.
- Blancou P, Vartanian J, Christopherson C, Chenciner N, Basilico C, Kwok S, Wain-Hobson S (2001). "Polio vaccine samples not linked to AIDS". Nature 410 (6832): 1045–1046. doi:10.1038/35074171. PMID 11323657.
- Berry N, Davis C, Jenkins A, Wood D, Minor P, Schild G, Bottiger M, Holmes H, Almond N (2001). "Vaccine safety. Analysis of oral polio vaccine CHAT stocks". Nature 410 (6832): 1046–1047. doi:10.1038/35074176. PMID 11323658.
- Rambaut A, Robertson DL, Pybus OG, Peeters M, Holmes EC (2001). "Human immunodeficiency virus. Phylogeny and the origin of HIV-1". Nature 410 (6832): 1047–1048. doi:10.1038/35074179. PMID 11323659.
- Poinar H, Kuch M, Pääbo S (2001). "Molecular analyses of oral polio vaccine samples". Science 292 (5517): 743–744. doi:10.1126/science.1058463. PMID 11326104.
- Korber B, Muldoon M, Theiler J et al. (2000). "Timing the ancestor of the HIV-1 pandemic strains". Science 288 (5472): 1789–96. doi:10.1126/science.288.5472.1789. PMID 10846155.
- Salemi M, Strimmer K, Hall WW et al. (2001). "Dating the common ancestor of SIVcpz and HIV-1 group M and the origin of HIV-1 subtypes using a new method to uncover clock-like molecular evolution". FASEB J. 15 (2): 276–8. doi:10.1096/fj.00-0449fje. PMID 11156935.
- Sharp PM, Bailes E, Chaudhuri RR, Rodenburg CM, Santiago MO, Hahn BH (2001). "The origins of acquired immune deficiency syndrome viruses: where and when?". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 356 (1410): 867–876. doi:10.1098/rstb.2001.0863. PMC 1088480. PMID 11405934.
- Worobey M, Gemmel M, Teuwen DE et al. (October 2008). "Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960". Nature 455 (7213): 661–4. doi:10.1038/nature07390. PMC 3682493. PMID 18833279.
- "News Africa". Reuters.com. Retrieved 2008-10-05.
- Lemey P, Pybus OG, Rambaut A et al. (July 2004). "The molecular population genetics of HIV-1 group O". Genetics 167 (3): 1059–68. doi:10.1534/genetics.104.026666. PMC 1470933. PMID 15280223.
- Weiss RA (2001). "Polio vaccines exonerated". Nature 410 (6832): 1035–1036. doi:10.1038/35074222. PMID 11323649.
- "HIV-1 in 1908?" AidsOrigins
- Nigeria Muslims oppose polio vaccination BBC News 27 June 2002
- Rumor, Fear and Fatigue Hinder Final Push to End Polio Celia W. Dugger and Donald G. McNeil Jr. New York Times 20 March 2006
- Jegede AS (2007). "What led to the Nigerian boycott of the polio vaccination campaign?". PLoS Med. 4 (3): e73. doi:10.1371/journal.pmed.0040073. PMC 1831725. PMID 17388657.
- BBC News (2005) "Anti-polio vaccine Malians jailed" online
- Cohen, Jon (2000) Atlantic Monthly (Oct), p. 104.
- Global Polio Eradication Initiative (2007) Map of last six months of polio cases worldwide Wild Poliovirus Weekly Update initiative of WHO, CDC, UNICEF, Rotary International online
- BBC News (2007) "Bangladesh begins new polio drive" online
- AIDSorigins.com: Edward Hooper's website on the OPV AIDS hypothesis
- Where did HIV come from? Questions and Answers, from the United States Centers for Disease Control