Lancet, September 25, 1999; Volume 354, Number 9184
Edward Hooper's river -- at 1000 pages, more Amazon or Congo than Thames -- is the AIDS epidemic in full flood, but what interests him is the trickle with which it all began. What also interests both him and the Oxford evolutionary biologist W D Hamilton, who writes the enthusiastic foreword to this provocative book, is what lessons might be drawn if the origin of HIV/AIDS is indeed an instance of medicine gone wrong. The hypothesis, which in part at least is testable, is that one type of oral poliovaccine developed in the 1950s involved culture in kidney cells of chimpanzees. The chimpanzee simian immunodeficiency virus is the non-human one most closely related to HIV-1 and, the argument runs, it was via the vaccination campaigns in Africa in the late 1950s (and possibly elsewhere) that SIV reached man. After that came mutation to HIV and spread to eventual epidemicity via several routes, one possibility being Haitian technicians returning home after assisting the newly independent Congo republic. An iatrogenic disaster in other words, "bidding to prove itself more expensive in lives than all the human attritions put in motion by Hitler, Stalin, and Pol Pot" (Hamilton).
You may have heard of this idea before, and Hooper gives full credit to those such as Tom Curtis (whose article in Rolling Stone prompted legal action) and the mysterious Louis Pascal, who ventured into the territory before him. He litters his prose with "may", "perhaps", and "possibly", but he has made up his mind. ". . . herein lies the truth. I believe that this is how the AIDS epidemic began", he concludes, and his summary lists 27 points in favour of the hypothesis but only four against. He has been patient as well as thorough. There are too many people involved over the 40 or so years of this story for there to have been a planned conspiracy of silence. However, Hooper's interviews, a demanding schedule spread over continents, were sometimes frustrating as he found doors once thrown wide in welcome now opened suspiciously at a second visit. And then there were puzzling gaps in files, the involvement of lawyers, and, more understandably after all this time, lots of "don't remember" and candidate interviewees dead.
To those who label this research dismissively as "archival" and without relevance to the clinical challenge of AIDS today or who fear the damage that might be done to polio and other vaccination programmes, Hooper (and Hamilton) counter that there are warnings for AIDS vaccine development and for activities such as xenotransplantation, where the threat of porcine endogenous retroviruses still causes concern. Much of Hooper's research is archival, in the library of the London School of Hygiene and Tropical Medicine or in the files, photograph albums, and memories of yesteryear.
The earliest confirmed HIV-1- positive blood sample is one taken in 1959 for another purpose from an African living in or near Leopoldville (Kinshasa). A host of HIV-positive bloods from, say, the 1940s would have killed off the poliovaccine theory. Nor can any hypothesis that disease X is caused by factor A survive a reliable report of X before A arrived, which is why Hooper so carefully looks at claims for older "AIDS cases". The "Manchester seaman", for example, died in 1959 having fallen seriously ill the year before. A clinical puzzle when recorded in The Lancet in 1960, this patient was to acquire both an ill-founded exotic travel history and a false-positive HIV status. Not AIDS, then, but perhaps what would today be called idiopathic CD4+ T-cell lymphocytopenia.
As far as the records and recollections will allow him -- and the lack of certainty about which cells were used in the suspect oral poliovaccine work decades ago is tantalising -- Hooper pursues the vaccine side of the story just as thoroughly. Under the microscope he also puts vaccine development and immunisation programmes outside the Congo, including immunisations at two special institutions in the USA. However, it is the Congo river and the coincidence of SIV, chimpanzee tissue culture (possibly), early HIV seropositivity and early AIDS, and terminal colonial exploitation that command most attention.
The onus of proof ought to lie with Hooper, though one can sympathise with his attempts to shift that burden to those on the other side. "Let them", he writes "come up with some material or documentary evidence that demonstrates that this theory is wrong". A key test, which the author himself cannot do, is to look for SIV/HIV independently in the only known surviving samples of the suspect vaccine in the freezer in Philadelphia and Stockholm. To another key question -- were chimpanzee kidneys used or not? -- all I can say is that if Hooper has not found the answer, will anyone, other than by testing the same samples for mitochondrial DNA? If tests on the Wistar Institute sample were to prove negative would Hooper surrender? Samples of the vaccines have been tested for SIV and HIV in Sweden and found negative. ". . . a blow to the theory", Hooper admits, but then spoils it by adding "[we] had never really expected that we would receive a letter informing us of a positive result -- that SIV or HIV had been found in CHAT vaccine".
This is a very long book, even without the notes and references (175 pages of them). Structurally, the author faced a difficult choice -- should he see separate parts of the argument through to the end every time, which might have allowed conciseness, or should he return to them as new information arose, thus recording more or less chronologically his own journey upstream? He seems to have opted for the latter, unwisely I think. The timing of the switch from SIV to HIV-1 and the arrival at around the same time of the three groups of HIV-1 (HIV-2 is covered too) require careful explanation if a late 1950s poliovaccine is to be found guilty. The scattered fashion in which the "molecular clock" discussion is set out in The River may prove to be a weakness. Oral infection is not the usual route for HIV transmission although in certain circumstances it can happen. The chapter on infection by mouth wanders far from this topic, another example of the author's problem with structure. There will also be readers irritated by the occasional irrelevance and travelogue style. Does it matter if one researcher wears jeans while her female colleague along the corridor dresses more conservatively or if the "waves made light, careless slaps as they fell on the shallow sands"?
So far, Hooper's hypothesis that AIDS is an iatrogenic illness has not captured the headlines I was expecting. No bad thing, perhaps, if it allows more considered appraisal of his arguments as against alternative explanations such as the monkey hunter/butcher theory set out earlier this year (Nature Feb 4, 1999, pp 385 and 436) and discussed in Hooper's postscript. Virological opinion currently runs against the oral poliovaccine theory. Perhaps that consensus will shift once the book has been read, an action I recommend to anyone who does not insist that a good detective story has to end with handcuffs.
Polio vaccines and the origin of AIDS
in the section on The River.
It is located on the website on suppression of dissent.