BioWorld International Correspondent

LONDON - The hypothesis that humankind could have unwittingly triggered the AIDS pandemic by administering oral polio vaccine made using chimpanzee cells is a shocking one. It now appears, however, that the theory is without foundation.

Four papers published last week report studies that pour cold water on the idea. Three teams of researchers looked for chimpanzee DNA in samples of the vaccine that had been used more than 40 years ago in what is now the Democratic Republic of Congo. They found none. One of these teams also looked for nucleic acids related to HIV-1. Again, their search drew a blank.

In the fourth paper, scientists described their study of the molecular evolution of the human immunodeficiency virus Type 1 to test whether the huge diversity of HIV-1 strains globally resulted from many different transmission events from chimpanzees to humans (as would have occurred if oral polio vaccine had been a source of infection). These researchers concluded that the observed variation was more likely to have been the result of the virus" being exported from the region to other parts of the world, on several occasions.

Commenting on the clutch of new studies, Robin Weiss, of the Department of Immunology and Molecular Pathology at University College London in London, wrote in Nature that "those of us who were formerly willing to give some credence to the [oral polio vaccine] hypothesis will now consider that the matter has been laid to rest."

In a Nature "News & Views" article titled "Polio vaccines exonerated," Weiss concluded that "some beautiful facts have destroyed an ugly theory."

At a superficial level, the hypothesis that one of the early polio vaccination programs could have inoculated tens of thousands of people with a simian version of HIV was an attractive one. For example, in the late 1950s, oral polio vaccine was given to people in Leopoldville (now Kinshasa), coinciding neatly with the earliest blood sample known to contain antibodies to HIV, which had been taken from an adult in Leopoldville in 1959.

First promulgated by the journalist Tom Curtis in Rolling Stone magazine in 1992, the theory was pursued by Ed Hooper, a journalist based in the UK. Hooper enthusiastically researched the origins of HIV, eventually publishing a book entitled, The River: A Journey to the Source of HIV and AIDS. In his book, Hooper suggests that the early oral polio vaccine had been grown in chimpanzee cells taken from animals that had been infected with the chimpanzee variety of simian immunodeficiency virus, known as SIVCPZ .

The researchers who made the vaccine batches, who included Hilary Koprowski, the former director of the Wistar Institute in Philadelphia, said that no chimpanzee tissue had been used to grow the virus, only monkey cells.

Hooper, backed by his mentor the late Bill Hamilton, an evolutionary biologist, called in his book for samples of early batches of polio vaccine to be tested independently to look for traces of HIV or SIV.

It is these studies that have now been carried out and published. A team led by Simon Wain-Hobson of the Pasteur Institute in Paris, reports in Nature that they found no trace of nucleic acids from HIV-1 in five samples of oral polio vaccine supplied by the Wistar Institute, including that used to vaccinate 75,000 people in Leopoldville.

In their paper, titled "Polio vaccine samples not linked to AIDS," they describe how they identified, during further experiments, DNA in most samples of the vaccine that belonged to the rhesus monkey (Macaca mulatta) or the cynomolgus monkey (Macaca fascicularis). Even using very high-resolution tests, they found no trace of chimpanzee DNA.

A second paper in Nature is from a team led by Neil Berry of the National Institute for Biological Standards and Control at Potters Bar in the UK, together with colleagues at the Karolinska Institute in Stockholm, Sweden. In a communication titled "Analysis of oral polio vaccine CHAT stocks," this group reports studies carried out on two samples of vaccine held in store at the NIBSC.

The first had been received from the Karolinska Institute in 1981, having been originally sent there from the Wistar Institute in 1958. The second had been made at the Institute of Immunology in Zagreb, in the former Yugoslavia, and sent to the NIBSC in 1987. Tests showed that both samples still contained viable attenuated poliovirus.

The UK/Swedish team set out to detect HIV and its variants, including SIVCPZ and the type of HIV that had been isolated from the 1959 Leopoldville sample, using primers for the polymerase chain reaction designed to detect such genetic material. They found no trace of HIV or SIV in either sample.

In further experiments, they looked for chimpanzee DNA, using primers designed to amplify this type of genetic material. Again, they drew a blank. Additional analysis allowed them to conclude that the cells used to prepare the vaccine batches were from rhesus macaques and cynomolgus macaques.

Svante Paabo and colleagues from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, report a series of similar experiments in Science, in a paper titled "Molecular Analyses of Oral Polio Vaccine Samples." These researchers were supplied by the Wistar Institute with 14 samples of vaccine to analyze for the presence of chimpanzee DNA. This study, too, found no evidence of chimpanzee DNA, only that from monkeys.

Paabo's team concludes in Science: "Obviously, the samples tested in this study represent only one of maybe four vaccine batches produced by the Wistar Institute and used in the Congo. However, the results at present give no support for the hypothesis that chimpanzee cells were used to produce the [oral polio vaccine] administered in the Congo in 1958 and 1959."

Hooper was not available last week for comment.

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