THE RIVER

A Journey to the Source of HIV and AIDS

By Edward Hooper

Little, Brown. 1070 pp. $35

Reviewed by Charles van der Horst

Visualize a striking symbol of benevolent colonialism in 1958: In the former Belgian Congo, beneath a broad pith helmet, a pale hand stretches out over a sea of upturned black faces and squirts a milky elixir into the open mouths. Now jump ahead to a picture of a child, with eyes looking down in a dusty, deserted banana plantation, surrounded by piles of rocks covering graves, a symbol of the 700,000 children orphaned this year by HIV infection. These are two images that The River attempts to link.

This book explores the hypothesis that the AIDS epidemic originated in that elixir, an early version of the live attenuated (modified) oral polio vaccine. The author proposes that an experimental vaccine used between 1957-60 was accidentally contaminated with a primate version of HIV. In the early 1950s Albert Sabin and Hilary Koprowski and others were racing to develop the first approved oral polio vaccine. Other than fame and glory for the scientists, the stakes were high: Polio was a frightening prospect for middle-class America; families kept their children home and away from swimming pools to avoid the dreaded, paralyzing disease. In the newspapers pictures of children in huge iron cylinders, "iron lungs," struck terror in mothers' hearts. Against this backdrop large-scale oral polio vaccine trials were begun around the world. In the former Belgian Congo in central Africa (now the Congo, Rwanda and Burundi), the largest studies used an attenuated live virus vaccine developed at the Wistar Institute in Philadelphia by Koprowski to vaccinate approximately a million children. The location of the vaccination campaign is surprisingly similar to the geography of the early HIV infections.

The author of this tome, Edward Hooper, has devoted most of his career as an investigative journalist to pursuing this theory. Despite the explosive nature of its topic, this book is not going to keep the reader up late at night turning pages. It is exhaustively detailed, stretching to 851 pages of text, with another 219 pages of lengthy footnotes and references. Every false turn, every missing document, every late night journey on a bus to an obscure Belgian village is described to the growing weariness of the reader. Between these redundant and unnecessary sections are thrilling nuggets detailing the history of polio vaccine development, primatology, the rise of AIDS in Africa and around the world, and African history, with its enormous flux of population due to the onset of wars and industrial development at the end of colonial rule. Superb primary data consisting of tables, maps, graphs and phylogenetic trees provide a clear thread with which to follow the story. Dozens of interviews with the leading luminaries in virology, vaccine development and HIV provide glimpses into the excitement of science.

For the theory to be valid, a series of facts must be found: HIV-1 and HIV-2, the two main etiologic agents of the current epidemic, must be genetically very similar to Simian Immunodeficiency Virus, specifically chimpanzee SIV in the case of HIV-1 and sooty mangabey SIV in the case of HIV-2. There should be no cases of AIDS prior to the vaccinations. The vaccinations should have been given only in Africa in areas geographically similar to the areas where the first cases of AIDS occurred. SIV must be able to be infectious when given by mouth. The vaccine must have been contaminated with SIV. Chimpanzee cells in the case of HIV-1 and sooty mangabey cells in the case of HIV-2 must have been used to prepare the vaccines. Cells infected with SIV must have been in those simian tissues. Procedures to make the final vaccine (freezing thawing, trypsinization, filtering, etc.) must not have inactivated the SIV. The genetic differences between SIV and HIV should have been able to disappear in 40 years of mutations in humans. To confirm all nine points is the tall order that the author strives mightily to carry out.

Many of these points cannot be proved conclusively. Yes, there are striking similarities between the genetic structure of HIV-1 and SIV from chimpanzees. Yes, primate kidneys were used to culture polio virus, but there is no proof that chimpanzee kidneys were used. Yes, cells infected with SIV (macrophages and lymphocytes) can contaminate primary kidney-cell cultures. Yes, there is a striking correlation between the origin of AIDS and locations of vaccination campaigns in geography and timing. Yes, HIV can be transmitted orally. Yet new evidence suggests that the jump from primates to humans occurred before 1957. And there is no smoking gun -- i.e., there is no sample of vaccine that was given only in Africa that contains HIV. There are also some contradictory data, such as that the vaccine was often given to the investigators, animal handlers and their children or given in both the United States or Europe and the Congo, yet the early cases of AIDS occurred only in the Congo.

The book is littered with the grindings of the author's axe. On page 424 he leaves the impression that a child given the oral polio vaccine developed a major complication due to the vaccine only to correct it on page 707. He interviews more and more people until he finds one who confirms his theory, usually a child of a now-deceased investigator! Facts that contradict his theory are relegated to footnotes. Where there are no data, he leaps giant chasms like Evil Knievel in a single bound to drive his point home.

The chief alternative theory, that of natural transfer, has fewer steps. There is widespread hunting and consumption of primate meat in this part of Africa. There are many examples of viruses, parasites and bacteria infecting humans who hunt and or eat meat; this could be one more. Isolated, sporadic cases of AIDS blossomed into a wildfire spread by civil wars, widespread use of unsterile needles for injections of medicines and movement of populations from rural to urban areas, with disruption of normal family structures. It is doubtful that either theory can be proved beyond a reasonable doubt.

Those brave enough to read the book may miss the author's skips, stretches and leaps. Although the author addresses a vaccine that was never approved for use and is long dead and buried, he will confirm the paranoia about vaccines given today, which undergo a rigorous quality control by the Food and Drug Administration (FDA). Although quality control is only as good as yesterday's assay to detect contamination, vaccines have transformed the health of the population. Diseases that once had dramatic consequences, such as smallpox, have been relegated to history books.

Besides pushing his theory, Hooper bashes investigators for conducting research without proper consent, using prisoners and children with severe mental handicaps and using animals. Also, he well documents the investigators' general sloppiness. There is no documentation as to the type of culture material or even the country, let alone the continent, in which the vaccine lots were made. In Africa and elsewhere, the term "trials" was used loosely: There was no control group, no informed consent and no follow-up to look for complications or even efficacy (benefit). All of these are valid criticisms but less so given the state of research in 1950s. Practices that would be considered immoral if not illegal now were perfectly commonplace at that time.

This book once again raises the specters of Tuskegee and Willowbrook, where subjects were put at risk without informed consent as late as the 1960s. More recent reminders have been given by the National Institutes of Health Office for the Protection of Research Risks, which has been cracking down on universities conducting human research. This book should help us to understand that those who invite people to participate in clinical trials today must be committed to entering into a full, respectful partnership with both people and their communities so as to ensure that everyone involved is fully informed.

Charles van der Horst is a professor of medicine and infectious diseases and director of the AIDS Clinical Trials Unit at the University of North Carolina in Chapel Hill.