New York Times Review
THE DOCTOR'S WORLD
New Book Challenges Theories of AIDS Origins
[Review of The River: A Journey to the Source of HIV and AIDS ]
By LAWRENCE K. ALTMAN, M.D.
New York Times, Tuesday 30 November 1999, pp. D1, D6.
Is AIDS a disaster inadvertently brought on by humans that arose from early testing of a polio vaccine in Africa in the 1950's?
This provocative theory seemed far-fetched when it first came to public attention in an article in Rolling Stone in 1992. Most AIDS experts dismissed it after a scientific committee reviewed the theory and deemed the probability very low.
But that panel based its conclusion in part on a published finding that was later shown to be in error. And now a remarkable new book by a British journalist offers tantalizing clues to revive and expand the polio vaccine theory.
In "The River" (Little, Brown, $35), Edward Hooper suggests that an experimental oral polio vaccine might have been made with chimpanzee tissue contaminated with an ancestor of the virus that was to cause AIDS. Although he has no medical expertise, Hooper, 48, has done a prodigious amount of research since 1990. In 1,070 pages, including extensive footnotes, he builds a case based entirely on circumstantial evidence that he accumulated in hundreds of interviews and exhaustive library research.
He finds close coincidence in both time and place between the earliest cases of AIDS and the testing of an oral vaccine developed at the Wistar Institute in Philadelphia and, later, in two laboratories in Belgium.
From 1957 to 1960, the vaccine was given to a million people in what are now Rwanda, Burundi and Congo. If the experimental vaccine was contaminated, nothing could have been done about it because tests for the ancestor virus did not exist then. And it would have been a one-time event because standard polio vaccines were not made from chimpanzee tissues. Of 28 cases of AIDS acquired in specified towns in Africa through 1980, 23 were from the same towns where the experimental vaccine was given or within 175 miles of them. The area is the epicenter of the African epidemic, which is the worst in the world.
And there is precedent for a simian virus's lurking in polio vaccine: millions of Americans were inadvertently infected with such a virus, SV-40, in the 1950's and early 1960's. (Fortunately, it was not harmful.) But in 1967, several laboratory workers in Germany died from the newly discovered Marburg virus after it had been imported in African green monkeys. The virus is harmless for the monkeys but lethal for humans.
The similarities Hooper describes could be coincidence. "The River" does not prove his extraordinary theory, nor does it claim to. But it builds a sufficiently detailed case to require serious examination of his theory.
Attempts to find answers require extensive research, and in the book and in subsequent interviews Hooper has offered a long list of suggestions, including laboratory testing of the small amounts of vaccine that still exist after having been stored for more than 40 years. Because the vaccine may have degraded over the decades, performing all the proposed research might still not determine whether it accidentally touched off the AIDS epidemic. And even if a simian virus turned up in the stored samples, it would not prove that it started the epidemic.
Still, even if the vaccine thesis is disproved, Hooper's research has embarrassed scientists. He has found that leading researchers kept sloppy records and that prestigious peer-reviewed medical journals published reports that omitted crucial details.
Despite a diligent search, Hooper could turn up no records of what primate tissues were used to prepare the first experimental polio vaccines, which were tested mostly in Africa but also in the United States and Europe. Though the government requires more record keeping today, scientists say there is ample room for improvement.
With the exception of a negative review in the journal Nature, experts writing in scientific journals have praised Hooper's diligence and scholarship and the plausibility of the thesis, even if they are skeptical of it. In the journal Science, Dr. Robin A. Weiss, a leading virologist in London, wrote that Hooper had written the most exhaustive history of polio vaccine trials and early AIDS cases.
The Wistar Institute, the first independent medical research center in the United States, appointed the 1992 panel to examine the theory that its vaccine might have touched off the AIDS epidemic. Now it says it is trying to find independent experts to do what they were unwilling to do seven years ago, when the panel recommended testing the remaining stocks of the experimental polio vaccine. One aim is to detect evidence of simian cousins of H.I.V.-1, the virus responsible for the overwhelming majority of AIDS cases in the world. A second is to determine the primate species from which the vaccine was prepared.
Ever since American doctors first recognized AIDS in 1981, the origin of the viral disease has been a mystery. Scientists have dismissed many theories, including those that held that the Central Intelligence Agency or K.G.B. concocted it, because they lacked evidence or did not fit the facts.
What is known is that the earliest documented H.I.V.-1 infection is from 1959 in a man in Kinshasa in what was then the Belgian Congo, was later Zaire and is now Congo.
Scientists generally agree that H.I.V.-1 derives from a simian virus in chimpanzees. But the unanswered question is how the virus jumped to humans. The usual view is that passage must have occurred in blood-to-blood contact, like a bite or cut during the slaughter of chimpanzees.
But humans have killed chimpanzees for centuries. So why did transmission not occur until the late 1950's? The conventional explanation cites the vast social changes that occurred after World War II: mass migration, urbanization and sexual freedom.
Monkey cells were routinely used to make polio vaccines then and now. But Hooper theorizes that chimpanzees were also used to prepare the experimental polio vaccine. As circumstantial evidence, he points to a large colony of chimpanzees at the Lindi River in central Congo, where the primates were caught for research. (The river of the book's title is a metaphor for the search for the source of AIDS.) Only a small percentage of chimpanzees are believed to carry the H.I.V.-1 ancestor virus. But if chimpanzee tissues sent to a laboratory in Philadelphia or Belgium were infected, they might have found their way into one or more batches of experimental polio vaccine, particularly the strain known as CHAT, prepared at the Wistar Institute.
In such an event, H.I.V.'s simian ancestor might have grown in the batches of polio vaccine used in experimental trials only. When the vaccine was squirted into human mouths, the simian virus could have passed through a sore or ulcer and entered the bloodstream, subsequently to evolve into H.I.V.-1. From there it would have been transmitted through sexual or blood-to-blood contact.
Any contamination would have been accidental, because specific tests could not have been performed before 1985, when a simian counterpart of H.I.V. was first isolated.
Whether chimpanzee tissue was used should be easily confirmed or refuted by checking laboratory records and scientific journals. But Hooper said he could not find out precisely how the vaccine was made, and neither could the committee that the Wistar Institute appointed in 1992 to examine the theory.
The committee was justifiably skeptical of the theory, in part because British scientists had reported that a seaman from Manchester died of AIDS in 1959 and probably was infected for about 10 years, thus placing the origin of H.I.V.-1 before the development of polio vaccines. Also, the experimental Wistar vaccine had been given in Poland and Sweden, and AIDS was not reported there in the critical years.
Despite the committee's skepticism, it recommended that two independent laboratories test the remaining vaccine. In seeking such cooperation, Wistar officials found only one lab, at the federal Centers for Disease Control and Prevention, willing to do the work, so it was dropped because it would have been impossible to obtain confirmation, Dr. Clayton Buck, Wistar's deputy director, said in an interview.
The testing has taken on new urgency because further research has shown that the Manchester man did not die of AIDS: that the H.I.V. thought to have been isolated from his body was actually from someone else infected more recently.
Nevertheless, the misdiagnosis of AIDS in the seaman does not alter any of the committee's other conclusions. Even if chimpanzee tissue was used, the vaccine theory remains a long shot, the head of the committee, Dr. Claudio Basilico of New York University, said in an interview.
Still, the committee was so concerned about the theoretical dangers from primate tissues that it urged vaccine manufacturers to make "a serious effort" to stop using them.
Dr. Basilico says his committee may be reactivated to oversee the preparation of the stored vaccine for testing. And the Wistar Institute has pledged to find two or three independent laboratories to do the tests.
"It ought to be done because it can be done," Dr. Basilico said, though he added that the testing might not provide a conclusive answer, in part because of the difficulty of disproving a theory.
In preparing the material for the independent laboratories, the Wistar Institute will include samples other than polio vaccine for purposes of scientific controls. The committee will code all the material to keep the testing laboratory from knowing which is which, Dr. Basilico said.
The Wistar polio vaccine was also given to a small number of Swedes. When some of the remaining vaccine was tested in 1995 as a result of Hooper's work, Swedish scientists found no evidence of simian viruses in it. But the findings do not refute the theory, because different vaccine batches may have been used in Africa and Sweden. Nor did the Swedish scientists try to determine the source of the primate species for the vaccine. Dr. Hans Wigzell, the director of the Karolinska Institute in Stockholm, said in an interview that he was skeptical of the vaccine theory but assumed the Swedish government would be willing to do more laboratory testing to try to find out.
Hooper's recommendations go beyond such testing.
One proposal is to conduct a formal investigation into the missing information and how the vaccine was made. If the precise technique could be determined, then scientists could investigate whether a contaminating simian virus was capable of surviving the vaccine-making process.
A second recommendation is to conduct a vast search of blood and tissues for evidence of H.I.V. in blood or tissue taken before the polio vaccine era; detecting the virus would strongly challenge the vaccine thesis.
A third proposal is to find out whether another early case of H.I.V., in a baby born in 1973 to a teenager in New Jersey, could have been linked to the testing of the experimental vaccine at a women's prison in Clinton, N.J.
With 16 million people dead and 33 million more infected, AIDS is among the worst epidemics in history. A seriously researched theory about something so devastating deserves a full scientific investigation even if the theory is unlikely and chances of proving or disproving it are slim. Since the credo of science is to seek the truth, science should assure the public of its integrity.
Vaccines are unquestionably one of medicine's great triumphs, and they have nearly eradicated polio from the world. But if experimental batches of polio vaccine were inadvertently contaminated with an ancestor of the AIDS virus when immunizations were made by much cruder techniques than those used today, then scientists and government officials would have to accept responsibility for a historic blunder.
Yet many scientists say privately that publicizing Hooper's theory would risk tarnishing public confidence in the safety of vaccines. Scientific groups that could have sponsored scientific meetings to discuss the vaccine theory, or taken an interest in testing the vaccine, have not done so. Hooper said an official of the World Health Organization told him that the origin of AIDS was "certainly of no interest today."
But that attitude is surely shortsighted. As Dr. Peter Piot, the head of the United Nations AIDS program, said in a recent interview, "If it were possible to determine where AIDS came from, that would be important for science and the world to know.