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Oral polio vaccine AIDS hypothesis

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Main articles: AIDS origin and AIDS origins opposed to scientific consensus

The oral polio vaccine (OPV) AIDS hypothesis argues that the AIDS pandemic originated from live polio vaccines prepared in chimpanzee tissue cultures and then administered to up to one million Africans between 1957 and 1960 in experimental mass vaccination campaigns.[1][2]

Data from molecular biology and phylogenetic studies contradicts the OPV AIDS hypothesis; consequently, the majority of the scientific community regards the hypothesis as disproven,[3][4][5][6] with an article in the journal Nature describing the hypothesis as "refuted".[7] Another potential human pathogen however, known as SV40, has been confirmed as present in polio vaccines cultivated from monkey tissues at around the same time.[8] Whether or not SV40 actually causes disease in humans however also remains highly controversial.[9]

Background: Polio vaccines

Further information: Polio vaccine

Two vaccines are used throughout the world to combat polio. 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.[10] 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.[10]

Both vaccines have been used for decades to induce immunity to polio, and to stop the spread of the infection.[11] 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.[11] Hence, OPV not only prevents paralytic poliomyelitis, but also, when given in sufficient doses, can abort a threatening epidemic. Other benefits of OPV include ease of administration, low cost and suitability for mass vaccination campaigns.[10]

CHAT vaccine

Oral polio vaccines were developed by several groups, one of which was led by Albert Sabin. Another group, led by Hilary Koprowski, developed its own attenuated vaccine strains. In 1952 Koprowski developed the TN strain at the Wistar Institute in Philadelphia, later identified as type 2 poliovirus. A type 1 strain, called SM, was reported in 1954. A less virulent version of the SM strain was reported by Koprowski in 1957.[12] The name of the vaccine strain was “CHAT” after "Charlton", the name of the child who was the donor of the precursor virus.[12] In 1958, the National Institutes of Health created a special committee on live polio vaccines. The various vaccines were carefully evaluated for their ability to induce immunity to polio, while retaining a low incidence of neuropathogenicity in monkeys. Based on these results, the Koprowski strains were eliminated and the Sabin strains were chosen for worldwide distribution.[13]

Between 1957 and 1960, however, Koprowski would continue to administer his vaccine around the world. In Africa, the vaccines were administered to roughly one million people in the Belgian territories, now the Democratic Republic of the Congo, Rwanda and Burundi.[12] No one is certain how many people were vaccinated in the Africa trials as few records remain -- but 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)[14]

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,[15] next a review of safety and efficacy,[16] then a 21-month follow-up and final report.[17] An epidemic of polio erupted in Leopoldville two months after the vaccination campaign began and continued at low levels for at least the next 19 months; many dozens of children who had been vaccinated developed paralytic polio. During this same period, Koprowski immunized 40,000 children in Germany and more than seven million in Poland with his attenuated strains.[13]

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[18][19][20] were used to amplify the virus at local production facilities, in order to produce actual doses. It has been reported that specific 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.[21] 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.[22]

Developments of hypothesis

San Antonio physician Eva Lee Snead was the first person to propose the hypothesis that AIDS could have crossed to humans via an infected polio vaccine.[23]

In May 1987, Louis Pascal heard a radio broadcast by Dr. Snead explaining her hypothesis. Based on information in medical journals published in the 1950s and 1960s, and the information about the first cases of HIV infection, he concluded that Dr. Hilary Koprowski's CHAT Type 1 vaccine administered in Belgian Congo between 1957 and 1960 was a likely source;[23] he dismissed contradicting evidence as "clear attempts at whitewash".[24] Pascal's paper about the hypothesis was submitted to several journals, but rejected by all. In their reply, Nature stated that: "While the theory cannot be ruled out, it does not seem readily to fit the epidemiology of AIDS."[23] In 1992 Pascal's paper was published by the University of Wollongong.[23] Pascal accused the medical journal editors who rejected his article of being "entirely culpable" in "sending who-knows-how-many present and future people to a horrible and pointless death" without any "conceivable excuse".[24] In 1992 the editor of the Journal of Medical Ethics acknowledged the importance of Pascal's paper, while declining to comment on the "truth of falsity" of his claims, and presented a summary of its content.[24]

In 1987, Blaine Elswood, a medical researcher into HIV,[25] who had developed similar ideas, contacted the journalist Tom Curtis about a "bombshell story." Curtis investigated the story and published an article on the OPV AIDS hypothesis in Rolling Stone in 1992.[26] In response, Hilary Koprowski sued Rolling Stone and Tom Curtis for defamation. The magazine published a clarification which praised Dr. 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.[27]

Rolling Stone was ordered to pay $1 USD in damages whilst incurring around $500,000 USD in legal fees for its own defense;[28] the legal action cost Dr Koprowski around US$300,000. A contemporaneous defamation suit that Dr. Koprowski brought against the Associated Press was settled several years later under undisclosed terms.[29]

A few scientists, notably the biologist W.D. Hamilton, thought the hypothesis required serious investigation, but they received little support from the scientific community. Hamilton wrote a letter to Science in 1994[30] supporting Pascal and Curtis, but it was rejected by the editors.

Journalist Edward Hooper, who had already begun to investigate the origin of AIDS when the OPV hypothesis was first put forward gradually became convinced of its truth. After nine years of investigations, he detailed the hypothesis and evidence in his 1999 book, The River. Hooper further expanded on these 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.[31] In 2001, Dr. Hilary Koprowski responded by making a detailed rebuttal of the points made in the book, also in a talk to the Royal Society.[32] However in 2004, the Origin of Aids, a TV documentary strongly supportive of the OPV hypothesis, appeared on television stations globally.

The Laboratoire Médical de Stanleyville was sited at the city now known as Kisangani

In 2003, Edward Hooper published additional statements that he believed supported his hypothesis in an article in the London Review of Books.[33] 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,[34][35] 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.[22]

In his book Hooper also stated that Dr Gaston Ninane was involved in using chimpanzee cells to produce vaccine in Congo. Dr Ninane responded to this allegation by stating that he could "categorically deny" ever having tried to make tissue cultures from chimpanzee cells.[12] 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.[22]

Scientific investigation

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) in 1959.[36] The reporting authors state,

"Multiple phylogenetic analyses not only authenticate this case as the oldest known HIV-1 infection, but also place its viral sequence near the ancestral node of subtypes B and D in the major group, indicating that these HIV-1 subtypes, and perhaps all major-group viruses, may have evolved from a single introduction into the African population not long before 1959."

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 October 1992, the journal 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 panel also noted that at least one case of HIV/AIDS was described prior to the OPV trial, (this claim, while scientifically accepted at the time, was later found to be factually incorrect. The error was caused by laboratory contamination.[37] ) and concluded that:

...it can be stated with almost complete certainty that the large polio vaccine trial... was not the origin of AIDS.[38]

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.[39] At this meeting, three independent labs ran tests on the remaining stocks of Koprowski's vaccine, as demanded by Edward Hooper 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; however it is important to note that these batches were not the ones prepared on-site in Africa. This prevents the test from disproving the hypothesis in and of itself.[39] 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."[39] 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.[39]

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.[40][41][42][43] 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.[44][45][46] These results were confirmed by a later study using samples from the 1960s that also found that the epidemic began between 1908 and 1930,[47][48] 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).[49]

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."[5] 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.[50]

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.[7]

Edward Hooper responded to these studies by either denying their relevance to the OPV hypothesis, or disputing their accuracy. For example, in response to the finding that chimps around Kisangani do not carry the ancestor virus to HIV Hooper stated that the chimps that he believes were used to produce vaccines came from a large area of Sub-Saharan Africa and that the specific line of chimpanzee that provided the precursor strain of SIV may have now gone extinct.

Current oral polio-vaccine campaign in Africa

It should be noted that the debate over the OPV-AIDS hypothesis is in the context of a 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 join smallpox to become the second infectious disease of humans to be eradicated everywhere, which should make subsequent polio vaccinations unnecessary. The OPV AIDS hypothesis relates only to the historical origin of AIDS, and its proponents accept the safety of the modern polio vaccines. Despite this, rumors based on a misunderstanding of the hypothesis exist,[51][52] and are blamed in part for the recent failure to eliminate polio in Nigeria.[53]

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 feared sterility the vaccine might induce in young women,[54] which seems irrational to most -- and it seems that debate over the OPV-AIDS hypothesis has fueled these sorts of fears among uninformed Africans.[55] 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”[53]

Now polio has also resurged in areas of Pakistan, India, and Bangladesh as well.[56][57] Other scientists, such as the late W.D. Hamilton of Oxford University, have argued that failures to adequately address medical mistakes of the past will only lead to similar failures in the future.[58]

See also

References

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  9. ^ See the article for SV40.
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  49. ^ Lemey P, Pybus OG, Rambaut A; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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  51. ^ Nigeria Muslims oppose polio vaccination BBC News 27 June, 2002
  52. ^ Rumor, Fear and Fatigue Hinder Final Push to End Polio Celia W. Dugger and Donald G. McNeil Jr. New York Times March 20, 2006
  53. ^ a b 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. PMID 17388657.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  54. ^ BBC News (2005) "Anti-polio vaccine Malians jailed" online
  55. ^ Cohen, Jon (2000) "The Hunt for the Origin of AIDS" Atlantic Monthly (Oct), p. 104; see also Ed Hooper's response online [1]
  56. ^ 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
  57. ^ BBC News (2007) "Bangladesh begins new polio drive" online
  58. ^ Hamilton W.D. (1994) "AIDS Theory vs. Lawsuit", letter submitted to the journal Science by the late Royal Society Research Professor at Oxford but rejected for publication at that time. online
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