Review of The River: A Journey to the Source of HIV and AIDS

Reviewed by Simon Wain-Hobson
Unité de Rétrovirologie Moléculaire, Institut Pasteur, 75724 Paris Cedex 15, France

The River: A Journey to the Source of HIV and AIDS
By Ed Hooper
Little Brown & Company, $35.00, 1104 pages ISBN 0316372617, 1999

A scientist's lot is not an easy one. Our job is to paint pictures and solve problems while learning the art at the same time. Reasoning and technical prowess are, in some ways, the easy parts. Creative thinking, linking discrete domains, conjuring up the big picture from only a handful of pieces is far harder. And yet these moments of clarity are exhilarating. However, for every idea that blossoms there are hundreds more that fall on barren ground. All this brings us back, once again, to human immunodeficiency virus (HIV).

The River is wide. The thesis: that the origins of both HIV-1 and HIV-2 result from contamination of poliovirus vaccines in the last half of the 1950s by simian immunodeficiency viruses of chimpanzees for HIV-1, or mangabeys for HIV-2. You read correctly. As the book is dominated by the origins of HIV-1 in central Africa, I will confine remarks to this. However, author Ed Hooper covers HIV-2 (and HIV-1 O and N for the aficionados). As HIV-1 is responsible for the pandemic, the essentials are covered. Although it is impossible to provide a précis of the 850 pages, the proposition boils down to whether the oral polio vaccine (OPV) preparations used by Hilary Koprowski - then director of the Wistar Institute, Philadelphia - and collaborators, particularly in Rwanda, Burundi and the north-east part of what was then the Belgian Congo, became contaminated with the simian immunodeficiency virus of chimpanzees (SIVcpz).

Instantly, one is reminded of the simian virus 40 (SV40) scare early in polio vaccination history. But is the OPV/AIDS connection remotely plausible? Yes. The spatial and temporal correlations between Koprowski's OPV program and very early AIDS cases are disturbing and this region is the disease epicentre. Is it likely? Perhaps. The alternative explanation of how SIV passed to humans is the 'wounded hunter' hypothesis, which posits that once upon a time a hunter cut himself, perhaps while preparing chimp meat. It is not clear to me what experiment can be done to test this; it seems unfalsifiable. In contrast, Hooper points out that the OPV/AIDS thesis is formally testable and goes on to make a list of suggestions at the back of the book as to how this could be done.

The River relates that near the Stanleyville (now Kisangani) base of Koprowski's African OPV operation, there was a big chimpanzee camp called Lindi. Upwards of 400 chimps passed through during the short life of the camp. Although some chimps were certainly used to test the safety of the trial vaccines, the fate of the vast majority is apparently undocumented. Hence Hooper asks what were the rest used for? It does seem that chimp kidneys were being excised and minced, and that some were sent to the US and Belgium, where Koprowski polio trial vaccines were made. And it seems that there is a dearth of information in Koprowski's papers from the 1950s describing the substrates used for trial vaccine preparations. Primary monkey kidney tissue cultures (that is, minced fresh kidney) were used. But which species of monkey? Occasionally chimpanzees as the book proposes?

In fact, the OPV/AIDS hypothesis goes back a few years and a number of authors have developed the theme. To my knowledge, none has collated more data, explored more ramifications, or interviewed more of the few remaining protagonists than Ed Hooper. The River cannot be seen merely as the latest reprinting of the idea, for it contains a vast amount of new research. Furthermore, some of the syntheses are as good as they come. I would give very high marks for his understanding of HIV virology and phylogenetics. Does he prove his case beyond a shadow of doubt? No, but then if Hooper could, this would be common knowledge. He does make a powerful case for soberly and squarely addressing the issue. He batters away at alternative hypotheses until OPV/AIDS is the sole survivor. Although many might not agree with his conclusions, the assault involves no sleight of hand. The approach is always well-documented; 176 pages of notes, to be precise. Put it this way, if you were to debate him, prepare yourself extremely well, for he either has an elephantine memory, or knows how to organize data. The tone is remarkably balanced, and he bends over backwards to point out where the data are insufficient. Even with the benefits of hindsight, he has avoided, fortunately, the insufferable path of the self-righteous.

The River is easy reading; the English, agreeable. The wealth of data might frighten some, but it should not deter. The interviews with many of the now-elderly participants are invariably revealing of the period. Amusingly, they are laced with allusions to food and coffee that conjure up images of Simenon's Inspecteur Maigret. Could the book have been shorter? Undoubtedly. It is written much like a travel journal, which no science editor would allow. Yet a river does not flow in a straight line. That is what makes it what it is. And so The River takes its course and we have no choice but to follow it, meanderings and all. The diversions into ox-bow lakes and small tributaries are, in the words of the Michelin guide book, worth the detour. But the current is never lost. A few times I was tempted to skim paragraphs. Big mistake.

Is there an issue, given that the AIDS pandemic is far from abating? After all, there are no vaccines or cheap drugs. Furthermore, it comes at a time when, thanks to OPV, there is much talk of pushing polio into the past tense, along with smallpox. Point taken. Yet the breadth of opinion in the current glut of books on virus evolution, or on emerging viruses, is showing us that we do not have a "unified field theory" of virus evolution and that nasty things can, and occasionally do, come out of the woodshed.

In contemplating the OPV thesis, many of those interviewed by Hooper considered the hypothesis tantamount to a disservice to medical science. Many stressed that past events could not be properly judged, or understood, under the blinding spotlight of today. Point taken - to some extent. But this is tantamount to saying that the history of an epoch stops with the death of its last contemporary chronicler. Furthermore, there is a world of difference between judging and wanting to learn what happened. Although this may be painful to some, it seems to me that the origin of AIDS is a story that will not go away - not until we have a solution consistent with the epidemiology and phylogenetics of the immunodeficiency viruses. The OPV/AIDS thesis is not inconsistent with the phylogenetics.

The downside, as opposed to the 'sad side', is that the hypothesis is seven years old. A wall of hostility or litigation has confronted almost every exponent - say no more. Although a scientific committee was set up to investigate, it seems that its report did not cover all aspects, essentially leaving the issue open. Sure, we all have more immediate things to do. Yet that is no licence for hostility. In the last chapters, Hooper describes the dangers of not facing up to difficult scientific and medical questions, from whatever quarter. With the mad cow debacle, to name but one example, there is some easy ammunition around. As Hooper has made a huge effort to document his thesis, it would be fitting if it had a sanguine hearing. If the suggestion is incorrect, then surely someone out there can dismiss it without too much fuss, with clear arguments supported by a modicum of data and references.

Hooper has upped the ante by a log. The search for the origins of HIV will not go away. The OPV hypothesis is formally testable, something which cuts both ways - Hooper could end up with 1,000 pages of egg on his face. But if reaction to The River is dismissive, or derogatory, then we shall see how hard it is for scientists, medics and institutions to address extremely difficult, sometimes painful, questions. Again.

In the words of Oliver Cromwell on the decision of the English Parliament to behead King Charles the First: "I beseech you in the bowels of Christ, think it possible you may be mistaken."