Up the River Without a Paddle?

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Review of The River: A Journey Back to the Source of HIV and AIDS by Edward Hooper Penguin: 1999. 1,070 pp. £25 (hbk)
Nature, Vol. 401, pp. 325-326, 23 September 1999

The theory that polio-vaccine researchers are responsible for AIDS is leaky.

Was John F. Kennedy shot from the grassy knoll by a Mafia hit man? Did HIV-1 enter humans via a contaminated oral polio vaccine (OPV) during mass vaccination campaigns in central Africa in the late 1950s? The second of these theories, the 'OPV-HIV' hypothesis, is the subject of this massive book by Edward Hooper which has attracted considerable media attention. The BBC even issued a press release with the inflammatory title "Scientists started AIDS epidemic".

The River is, in many ways, superb. It is scholarly, thoroughly researched, well (if densely) written and deserves, indeed demands, to be taken seriously. It takes the OPV-HIV hypothesis way beyond its early manifestations in the magazine Rolling Stone, and infinitely past the strange Internet discussions of Californian AIDS activists. These conspiracy theorists have given the hypothesis a bad name -- Hooper has redressed the balance by presenting careful and thorough research. His description of the early days of the African and Western AIDS epidemics is marvellous, but it is his support for the OPV-HIV hypothesis that will attract most attention.

The problem is that, like the grassy knoll theory, there is no smoking gun. Despite diligent investigation, Hooper cannot prove what he proposes and many of his arguments are highly speculative. Thus, a chain of events is outlined in which each link is weak. The argument goes like this. First, sick chimpanzees housed at Camp Lindi in the Congo in 1957-58 for use in medical research might have carried a primate immunodeficiency virus (PIV). Yet PIVs are not known to cause disease in chimps, and even if these animals were somehow infected with a pathogenic PIV, one could argue that any transmission to humans occurred by a more conventional route such as via blood during butchery procedures, or from biting or scratching during handling. Instead, Hooper suggests that "it could be that [kidneys from these chimps] ended up at the Wistar" -- a laboratory in Philadelphia where polio vaccines were manufactured -- where they contaminated vaccines with a PIV.

Chimp kidneys were shipped from Lindi to Philadelphia in 1958 and 1959. But they went to an institute doing hepatitis research, not to the Wistar, and the surviving Philadelphia- and Congo-based scientists deny that polio vaccines were ever made from chimp kidneys.

Second, the supposedly PIV-contaminated vaccine was then used in the Congo in 1957-58, transmitting the virus that evolved into HIV-1. Although PIVs can spread orally, it is unlikely that kidney-cell cultures, even if they did contain significant quantities of lymphocytes and macrophages, would produce much virus and that enough of this could survive storage and shipment.

Finally, the theory has the infected humans progressing to AIDS over the next 15-20 years, dying only around the time when the disease first became visible in central Africa in the mid-to-late 1970s. Again, this is possible, but not probable. The first authentic HIV-1 sequence, from the Congo in 1959, has characteristics making it unlikely that a chimpanzee virus, such as SIVcpz, first crossed to man only a few years earlier. A few decades is a more reasonable estimate.

One can sense Hooper's frustration that, despite all his work, he cannot prove his central point. He states "it could have happened this way", but can any of the complex sequence of events ever be proven? Hooper outlines a series of investigations, some of which are worthwhile. If additional records of polio-vaccine production exist, they should be released. And if frozen samples of the relevant vaccine stocks still exist in American or European institutions, these should be tested for the presence of possible HIV-1 precursor viruses. If the air of suspicion can be cleared, then it should be. But any such tests would have to be most carefully designed, executed and interpreted, and it is notable that some frozen vaccine stocks were analysed in Sweden in 1995, with negative results.

Hooper rightly argues for more research on the earliest stages of the HIV-1 epidemic in Africa and the West, with searches for archival tissues that could be analysed for HIV-1sequences. Certainly, more knowledge of the animal reservoirs for HIV-1 and HIV-2 would be useful, and might finally settle the issue of the origin of AIDS. But the need to address the past must be balanced against the more pressing requirement to prevent HIV-1 spreading -- by, ironically, the development of an effective vaccine.

Some of Hooper's proposals are less valuable. It would not, as he suggests, be informative to try to reconstruct the route of contamination. Experiments along these lines were performed in 1993 by John Garrett and colleagues in the United Kingdom. The results were negative. Even so, Hooper dismisses them as perhaps not reproducing the conditions used for polio-vaccine preparation in the 1950s. But could the conditions of 40 years ago ever be reproduced well enough?

The scientist most criticized in The River is Hilary Koprowski, formerly of the Wistar Institute. Many of Koprowski's actions and attitudes are presented in a very poor light. The accuracy of this portrayal can perhaps only be judged by those who know him. But even if the OPV-HIV link were correct, neither Koprowski nor anyone else would be to blame. The risks of cross-species viral transmission were much less well understood 40 years ago; one cannot condemn the past for not following the standards of the present. At worst, what Hooper argues happened would have been a tragic accident. What is it about AIDS that makes people seek a villain(s)? Do we blame anyone for the Black Death? Or for the influenza pandemic of 1919, a classic example of how animals are a reservoir for human viruses? Of course not. But in the AIDS epidemic, normal reasoning often gets discarded.

There are lessons to be learned from The River. One critical point is best made by a Philadelphia polio-vaccine researcher of the 1950s, who said "even though procedures [like vaccination] are very laudable and necessary, you do in fact have to make every possible effort to ensure that all safety procedures are satisfied". The theoretical and actual dangers of cross-species viral transmission are now clear, so absurdities such as baboon liver transplants into AIDS patients simply must be avoided in future. There can be few excuses today for meddling with viruses in such a potentially lethal manner.

My biggest concern over this book is that it could reinforce public distrust of science and scientists. It is a dangerous policy to hammer science for unproven -- and probably unprovable -- events. Eventually the public may turn to those who believe that science is bad for society. That really would be a tragedy.

So, while respecting Hooper's scholarship and thoroughness, I am not convinced by his central argument. At most, I turn to the Scottish legal verdict of 'Not Proven'. But an outright acquittal for the polio-vaccine researchers of the 1950s would be sounder, pending the discovery of solid, and not just circumstantial, evidence to the contrary. Instead, I believe that HIV-1 and HIV-2 crossed to humans from chimpanzees and sooty mangabeys, respectively, probably when PIV-infected animals were butchered for human consumption. Oh, and I also believe that Kennedy was shot by Lee Harvey Oswald from the sixth floor of the Texas Book Repository.

John P. Moore is at the Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Avenue, New York, New York 10016, USA.