Oral polio vaccine AIDS hypothesis

Background: polio vaccines

Two vaccines are used throughout the world to combat poliomyelitis. The first, a 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 formaldehyde 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 US 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. next a review of safety and efficacy, then a 21-month follow-up and final report.

Vaccine production

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, historian-turned-activist 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, virologist Hilary Koprowski, implicated in the article as being possibly involved in the early spread of AIDS, sued Rolling Stone and Tom Curtis for defamation. The magazine published a clarification which praised Koprowski and stated: Rolling Stone was ordered to pay US$1 in damages whilst incurring around US$500,000 in legal fees for its own defense.

A few scientists, notably the evolutionary biologist W. D. Hamilton, thought the hypothesis required serious investigation, but they received little support from the scientific community. For example, in 1996, Science refused to publish a letter Hamilton sent to it in which he replied to a 1992 Koprowski letter. Hamilton kept his position and said in 1999, "This theory, rather sadly, has gone from strength to strength. It's not proven by any means, but it's looking very strong." Hamilton was also supportive of journalist Edward Hooper who detailed the hypothesis in his 1999 book, The River. None of the over 60 urine and faecal samples collected by Hamilton contained SIV. 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, Hooper published additional statements that he believed supported his hypothesis in an article in the London Review of Books. These included accounts of an 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:

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:

Scientific investigation

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:

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 and was found with retrospective genetic analysis to be most closely related to subtype D strains. In 2008, partial HIV viral sequences were identified from a specimen of lymph node collected from an adult female, also in Kinshasa, in 1960. This specimen, named DRC60, was around 88% similar to ZR59, but was found to be most closely related to subtype A HIV-1 strains. These specimens are significant not only because they are the oldest specimens of the virus known to cause AIDS, but because they show that the virus already had an extensive amount of genetic diversity in 1960.

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."

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 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.

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, or that it is contaminated with HIV, based on claims made in The River. 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:

As evidence to the success of polio eradication efforts, the vaccine-derived polioviruses (cVDPVs) nowadays cause more cases of polio paralysis than the wild type virus itself in many places, such as the Congo. Polio has also resurged in areas of Pakistan, India and Bangladesh.

References

References

1. Weiss, R. A.. (2001-06-29). "Natural and iatrogenic factors in human immunodeficiency virus transmission". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.
2. Hillis DM. (2000). "AIDS. Origins of HIV". Science.
3. Birmingham, Karen. (2000-10-01). "Results make a monkey of OPV–AIDS theory". Nature Medicine.
4. (October 22, 2007). "Origin of Human Immunodeficiency Virus (HIV/AIDS)".
5. (2004). "Origin of AIDS: contaminated polio vaccine theory refuted". Nature.
6. "Debunked: The Polio Vaccine and HIV Link". The College of Physicians of Philadelphia.
7. (2005). "Vaccine-derived polioviruses and the endgame strategy for global polio eradication". Annu Rev Microbiol.
8. Pearce J. (2004). "Salk and Sabin: poliomyelitis immunisation". J Neurol Neurosurg Psychiatry.
9. Furesz J. (2006). "Developments in the production and quality control of poliovirus vaccines – Historical perspectives". Biologicals.
10. Plotkin SA. (2001). "CHAT oral polio vaccine was not the source of human immunodeficiency virus type 1 group M for humans". Clin. Infect. Dis..
11. Koprowski H. (July 1960). "Historical aspects of the development of live virus vaccine in poliomyelitis". Br Med J.
12. (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". Bull World Health Organ.
13. (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". Bull World Health Organ.
14. Enders, John. (1955). "Poliomyelitis". World Health Organization.
15. Rappaport, Catherine. (1956). "Trypsinization of Monkey-Kidney Tissue: Automatic Method for the Preparation of Cell Suspensions". Bull World Health Organ.
16. 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
17. 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?". [[Rolling Stone]].
18. (December 9, 1993). "'Origin of AIDS' update – Clarification".
19. Martin B. (August 2003). "Investigating the origin of AIDS: some ethical dimensions". J Med Ethics.
20. Bliss, Mary. (6 January 2001). "Origin of AIDS". [[The Lancet]].
21. (September 2001). "The Politics of a Scientific Meeting: the Origin-of-AIDS Debate at the Royal Society". [[Politics and the Life Sciences]].
22. (1 September 1999). "Scientists started Aids epidemic".
23. Bozzi, Maria Luisa. (29 September 2001). "Truth and Science: Bill Hamilton's Legacy".
24. (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..
25. Koprowski H. (2001). "Hypotheses and facts". Philos. Trans. R. Soc. Lond. B Biol. Sci..
26. Cecil Fox. (8 February 2022). "The Origins of AIDS (2004) video".
27. (2 May 2004). "Les origines du SIDA".
28. Osterrieth PM. (June 2001). "Vaccine could not have been prepared in Stanleyville". Philos. Trans. R. Soc. Lond. B Biol. Sci..
29. Osterrieth P. (May 2004). "Oral polio vaccine: fact versus fiction". Vaccine.
30. 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..
31. Koprowski. (1992). "AIDS and the Polio Vaccine". Science.
32. (1992). "Panel nixes Congo trials as AIDS source". Science.
33. (October 2, 2008). "Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960". Nature.
34. (12 September 2000). "Vaccine Theory of AIDS Takes a Blow".
35. (2001). "Polio vaccine samples not linked to AIDS". Nature.
36. (2001). "Vaccine safety. Analysis of oral polio vaccine CHAT stocks". Nature.
37. (2001). "Human immunodeficiency virus. Phylogeny and the origin of HIV-1". Nature.
38. (2001). "Molecular analyses of oral polio vaccine samples". Science.
39. Korber B. (2000). "Timing the ancestor of the HIV-1 pandemic strains". Science.
40. Salemi M. (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..
41. (2001). "The origins of acquired immune deficiency syndrome viruses: where and when?". Philos. Trans. R. Soc. Lond. B Biol. Sci..
42. "News Africa". Reuters.com.
43. Lemey P. (July 2004). "The molecular population genetics of HIV-1 group O". Genetics.
44. Cohen J. (2001). "AIDS origins. Disputed AIDS theory dies its final death". Science.
45. Weiss RA. (2001). "Polio vaccines exonerated". Nature.
46. (27 June 2002). "Nigeria Muslims oppose polio vaccination".
47. (20 March 2006). "Rumor, Fear and Fatigue Hinder Final Push to End Polio".
48. Jegede AS. (2007). "What led to the Nigerian boycott of the polio vaccination campaign?". PLOS Med..
49. (May 12, 2005). "Anti-polio vaccine Malians jailed".
50. Cohen J. (October 2000). "The Hunt for the Origin of AIDS". [[The Atlantic]].
51. Roberts, Leslie. (2018-07-02). "Alarming polio outbreak spreads in Congo, threatening global eradication efforts".
52. [[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 [http://www.polioeradication.org/content/general/casemap.shtml online] {{webarchive. link. (25 September 2006)
53. (March 2, 2007). "Bangladesh begins new polio drive".