Quest for the Origin of AIDS
Controversial book spurs search for how the worldwide scourge of HIV began
William
Carlsen, Chronicle Staff Writer A Simian Virus Jumped to Humans - But How?
First in a two-part series
Jan 14, 2001
Rogue virus in the vaccine
Did Modern Medicine Spread an Epidemic
http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2001/01/14/MN140641.DTL
The longer Edward Hooper studied the maps, the more he believed he had solved one of the great mysteries of modern medicine.
He had marked the Central African villages that were home to some of the earliest known cases of AIDS. In a striking number of cases, those villages were near the rural clinics where a U.S. company had tested one of the world's first oral polio vaccines in the late 1950s.
For nearly 10 years, the former BBC reporter had been investigating the possibility that something had gone terribly wrong during the vaccination campaign - that a monkey virus had contaminated the experimental polio vaccine and ignited the global AIDS epidemic.
It was a theory so troubling - and some say so riddled with flaws - that for years respected science journals refused to even acknowledge it. But when Hooper's book "The River" was published in late 1999, laying out evidence for the hypothesis in meticulous detail, the international scientific community could no longer ignore it.
Last fall, the Royal Society of London, the prestigious scientific academy once presided over by Sir Isaac Newton, called the first-ever conference on the origin of the AIDS epidemic, primarily to address the theory advanced by Hooper, a non-scientist who had majored in American literature in college.
The two-day conference drew some of the most prominent medical researchers in the world. By the time the historic showdown concluded, other rival and conflicting theories would emerge - including one involving the widespread use of contaminated needles - and Hooper would not be the only one to ask the chilling question:
Did modern medicine inadvertently cause one of the greatest scourges of the 20th century?
The answer will have significance for generations to come. More than 57 million people have been stricken with AIDS, 22 million have died, and 15,000 new infections are occurring daily. And experts now fear there are other lethal viruses out there in the "hot zone."
If AIDS did sweep the globe because of human error, perhaps the next, more devastating epidemic can be prevented.
The EPIDEMIC EMERGES
Los Angeles, 1981
In the spring of 1981, two doctors in Los Angeles reported to the Centers for Disease Control in Atlanta that they had discovered a rare kind of pneumonia caused by the bacteria, Pneumocystis carinii, in five recent patients. All five were gay men. Two of them had unexpectedly died.
More stricken patients followed. Doctors in Los Angeles, San Francisco and New York soon observed that something was destroying the immune systems of their gay patients. And the number of cases quickly began to rise.
That summer researchers at the National Cancer Institute in Maryland used a new, state-of-the-art medical device called the Fluorescent Activated Cell Sorter to test the blood of 15 apparently healthy gay men from the Washington, D.C., area. The results were disturbing - half the men had such severe abnormalities in their immune systems that the lab technicians thought the machine had malfunctioned.
As the cases accumulated and hundreds of patients continued to die, researchers were dumbfounded. They had no idea what they were dealing with. Was it a new venereal disease? Did it only affect gays? Where had it come from? And what could they do to treat their patients?
The only thing they knew for certain was that more would die before they had any answers.
Bethesda, Maryland, 1984
In the early years of the AIDS epidemic, theories attempting to explain the origin of the disease ranged from the comic to the bizarre: a deadly germ escaped from a secret CIA laboratory; God sent the plague down to punish homosexuals and drug addicts; it came from outer space, riding on the tail of a comet.
Then in 1984, researchers in Paris, San Francisco and at the National Cancer Institute in Bethesda, Maryland, isolated the elusive human immunodeficiency virus, HIV, that was causing AIDS.
Researchers soon learned that unlike quick-acting pathogens that cause smallpox, malaria or the flu, HIV can lie in wait for a decade or more before overtaking its victim's immune system and displaying its first symptoms.
For public health officials and epidemiologists, the isolation of the virus was a major breakthrough, leading to tests for the presence of HIV antibodies in a patient's blood.
Armed with the new tests, researchers began to track the movement of the slow-acting disease. By the first week of April 1984, more than 4,000 AIDS cases had been recorded in the United States. And new case reports were coming in from around the world - 33 countries so far.
University of California,
Davis, 1985
Monkeys were mysteriously dying, too.
For the past decade, Asian monkeys in research centers across the United States had been dying from outbreaks of opportunistic infections, and Preston Marx, a virologist at UC Davis, and other primate researchers were baffled.
Then when the first AIDS cases in humans were reported, Marx and others began to suspect that the monkeys were dying from a similar disease.
In 1985, researchers outside Boston isolated the virus that had been destroying the Asian monkeys' immune systems. It bore intriguing genetic similarities to HIV, so they called it SIV - simian immunodeficiency virus.
The primatologists finally traced the source of the virus to a species of medium-sized monkeys called sooty mangabeys for the ash-gray color of their coats. The mangabeys, which came from Africa, were often caged with the Asian monkeys.
The odd thing was that the mangabeys never got sick, even though they carried the virus and apparently gave it to the Asian monkeys. Was it possible,
Marx wondered, that the mangabeys had built up an immunity to the virus over thousands of years of exposure in the African rain forests? And if SIV could have originated in Africa, was it possible HIV had come from there, too?
Marx got out his monkey book and looked up the sooty mangabeys. They came from a narrow coastal range in West Africa.
Seattle, 1985
Soon after the first cases of AIDS were reported, medical researchers began casting back in time to try to find earlier AIDS cases, trying to calculate when and where the virus first infected humans.
Some of the earliest cases occurred in Haiti. One case involved a French geologist who had a blood transfusion in Port-au-Prince in 1978 and died of AIDS four years later. In another, the virus claimed the life of a former Canadian nun who worked among Haitian prostitutes and reportedly had a single sexual encounter some time before 1977.
But the trail soon led to Africa.
In 1985 researchers retested blood samples taken nine years earlier by a team of experts from the CDC that had rushed to Central Africa to contain an outbreak of a frightening new virus called Ebola. Five of the blood samples taken from local villagers tested positive for HIV.
That same year, researchers tested even earlier blood samples from the Congo. The blood had been collected by two doctors, an American and a Belgian, who had been investigating genetic differences in ethnic groups in Central Africa. The specimens had been flown back to Seattle for testing at the University of Washington and then stored in the laboratory's freezers.
In the 1985 retesting, Emory and Harvard University scientists used four different procedures on the samples and found one that was positive for HIV. The specimen, which came to be known as ZR59, had been taken from an unidentified African male from the area near Leopoldville (present-day Kinshasa) in 1959.
The sample would become famous as the earliest biological evidence of HIV in humans and a benchmark for all future researchers.
Lake Victoria, Uganda, 1986
In August 1986, Edward Hooper set off from Kampala, Uganda, to investigate an outbreak of a new disease that was striking down villagers along the swampy western shore of Lake Victoria.
Born in London's East End, Hooper had lived on and off in East Africa for nearly five years. As a backpacking university student, he became entranced with the region, and he later worked as a teacher, storekeeper and relief agency worker to stay on.
In the mid-1980s, he had returned to the region as a journalist and a part- time correspondent for the BBC. In Kampala, he heard talk that hundreds of people near the Tanzania border were sick and dying, and that medical experts believed they were suffering from AIDS.
Hooper had heard of gays, drug users and hemophiliacs stricken with the disease - but never entire communities - so he traveled to the lakeside hamlet of Kasensero to investigate.
One of the elders called a meeting under a tall tree so the villagers could tell Hooper about the illness that arrived four years earlier and had so far claimed nearly 100 lives.
There were coughs and fevers, sores and diarrhea, they said. But the final symptom was loss of weight, leaving its victims gaunt and shrunken. They called the new illness "slim."
When Hooper asked how they caught the illness, some said it came from witchcraft or was brought by Tanzanian soldiers who had come through the area seven years earlier. One villager heard on the radio about a similar disease in America and said the disease had been brought to Africa by whites.
Hooper filed several reports that were published around the world. And that hot August day began the journey that would culminate 13 years later with the publication of "The River."
"I still look back on that day with a mixture of sadness and horror," wrote Hooper, describing the scene in his book.
It would be many years before Hooper would understand the significance of the location of his Kasensero visit, but the theory that would come to dominate his life was just about to emerge.
New York City, 1987
Louis Pascal was tuned to radio station WABC in New York City when an interview with a doctor from San Antonio caught his attention.
For more than a year, Pascal had been working on a theory about the transmissability of HIV. Now, in May 1987, he listened intently as the doctor, Eva Lee Snead, described how monkey kidney tissue used to grow polio vaccines had been infected with a simian virus called SV40.
Snead theorized that SV40 was an ancestor of HIV and that the AIDS epidemic was caused by a mass immunization campaign with the contaminated vaccines.
Pascal, a reclusive figure whose published work consisted of a single essay in a philosophy anthology, decided to research the theory in a local library.
He found that Snead was at least half-right. In the late 1950s, SV40, at the time an undetected simian virus, had contaminated several polio vaccines, though there was little evidence the contamination had caused medical problems.
But Pascal found no evidence that the monkey virus was genetically related to
His research did, however, turn up a remarkable coincidence. The sites in Central Africa where an experimental oral polio vaccine had been administered between 1957 and 1960 were also ground zero for one of the greatest concentrations of AIDS cases in the world.
For months, Pascal pored over scientific journal articles and other documents, until he became convinced that there was a link between the vaccination sites and the earliest AIDS cases. And in November 1987, he drafted an article carefully laying out his theory.
For the next five years, he tried to publish that article and others. He sent the articles to biologists, AIDS researchers and scientific publications including Nature, Lancet and the New Scientist.
But all he got in return were rejections or silence.
Liberia, 1987
Across the Atlantic, Marx, the UC Davis virologist, drove slowly along the main roads of Liberia, a small nation on the west coast of Africa, searching for sooty mangabeys.
Liberia and neighboring Sierra Leone formed the natural range of the mangabeys, and Marx soon observed that hunters often killed the adult mangabeys in the forest, then brought them to market to be butchered for food. They also brought home orphaned infant mangabeys and kept them for pets.
Near the northern town of Zorzor, Marx stopped and snapped a photo of a 10- year-old girl holding a mangabey in her arms. Later he photographed a villager's pet mangabey named "Joe" sitting tamely on the back seat of his jeep.
During a number of trips over the next four years, Marx would collect blood samples from pet and wild mangabeys, as well as from villagers living in the northern and eastern parts of Sierra Leone.
When he returned to the United States, Marx found that some of the mangabey blood samples tested positive for SIV. And the blood samples from a few of the villagers contained both HIV and mangabey SIV genes.
Had the simian immunodeficiency virus jumped the species barrier from the mangabeys to villagers? Marx wondered. Could the virus have crossed over through a bite or blood splashed into a hunter's open cut when the monkeys were butchered for food?
And if the SIV had crossed the species barrier to African hunters and their families, Marx realized, it would have been going on for centuries.
West Sussex, England,
June 1992
Hooper leafed through a copy of the March 12 issue of Rolling Stone magazine until he found what he was looking for.
A freelance writer from Texas named Tom Curtis had written an article outlining a theory about the origin of the AIDS epidemic - essentially the same hypothesis Pascal had described five years earlier.
Curtis wrote about an oral polio vaccine that had been developed by Hilary Koprowski at the Wistar Institute in Philadephia. During the 1950s, Koprowski, a Polish emigre to the United States, and two other prominent scientists - Jonas Salk and Albert Sabin - had been fierce competitors in the race to find a vaccine that would wipe out polio.
Curtis wrote that the experimental vaccine that Koprowski developed had been given to 300,000 people in the Belgian Congo between 1957 and 1960 - the same area where the earliest known cases of AIDS have been found. And, according to Curtis, the kidney cells that Wister used to grow batches of vaccine might have come from monkeys infected with SIV.
Hooper was fascinated. During the past two years he had conducted 200 interviews while investigating 15 different AIDS origin theories, but he had heard only a brief, passing mention of the contaminated vaccine hypothesis.
Now he had a full explanation of the theory and it seemed far more plausible - and unnerving - than any hypothesis he had come across.
Hooper read every word of the article. When he finished, he took a long walk to calm down. Then he went home and read the article again.
New York, October 1992
Koprowski was furious.
The article in Rolling Stone had drawn widespread attention, particularly after a major wire service picked up the story and sent it around the world.
As far as Koprowski was concerned, the article threatened to destroy his life's work. He fired off a letter to Science magazine, vehemently dismissing the theory as "the wildest of lay speculation." Then he sued Curtis and Rolling Stone for defamation.
Meanwhile, the Wistar Institute assembled a panel of experts to investigate the central allegations in the Rolling Stone theory.
Six months later, in October 1992, the panel held a press conference in New York to deliver an eight-page report on their findings.
The six experts concluded that the chance that any SIV survived the vaccine tissue culture process "cannot be discounted" but any concentration of SIV particles would have been "extremely low."
Furthermore, the panel noted, oral transmission of SIV/HIV is "extremely rare," and the genetic age of HIV suggested that the virus had existed in humans many years before the vaccination campaign in the late 1950s.
But "the most telling evidence," the six-member panel concluded, "was the case of the Manchester sailor."
The sailor was a British printer named David Carr, who had served in the Royal Navy in the 1950s. In 1958 he was stricken with a mysterious illness and died a year later, suffering from a number of characteristic AIDS symptoms.
His puzzled doctors preserved 50 tissue samples in small paraffin blocks. When some of the specimens were examined in 1990, cells stored in the wax tested positive for HIV, making Carr the earliest known case of AIDS, apparently contracting the disease at least several years before the 1959 Leopoldville case.
The Wistar experts noted that Carr had completed his naval service and returned to England by early 1957 before the Wistar vaccination campaign had begun. "Therefore," the panel said, "it can be said with almost complete certainty that the large polio vaccine trial begun late in 1957 in Congo was not the origin of AIDS."
The report seemed to exonerate Koprowski. But the panel recommended that monkey tissue no longer be used in the manufacture of vaccines because of the risk of contamination from "other monkey viruses which have not yet been discovered."
It also suggested that independent tests be run on a remaining sample of the Wistar vaccine stock that may have been used in Africa to see whether it contained any SIV.
Later, Rolling Stone settled Koproski's lawsuit by publishing a clarification saying it never intended to suggest there was "scientific proof" the vaccine caused AIDS.
Oxford, England,
September 1993
Despite the findings of the Wistar panel, Hooper pressed ahead with his research, conducting further interviews and poring over all the records and eyewitness accounts he could find on the Wistar vaccine trials in Central Africa.
When he heard that a celebrated scientist, William Hamilton, was also intrigued by the polio vaccine theory, Hooper went to visit the professor at his cottage in a village near Oxford. It was a meeting that years later bore fateful consequences.
In 1992 and 1993, Hamilton had won three of science's most prestigious prizes for his work in evolutionary biology - the Wander Prize from the University of Bern, the Kyoto Prize from the Inamori Foundation and the Crafoord Prize from the Swedish Academy of Sciences. He was fascinated by the evolutionary aspect of the AIDS virus, particularly the fact that its apparent natural host, African primates, appeared to be immune.
The two men discussed the various theories about the origin of the epidemic, and Hamilton encouraged Hooper to continue investigating the vaccine theory despite the findings of the Wistar panel.
Hamilton was not impressed by the panel's report. Shortly after Hooper's visit, he wrote letters to Nature and Science, calling the report scientifically weak and preliminary.
What disturbed him the most, Hamilton wrote, was the scientific community's reaction against the theory, particularly the earlier refusal of periodicals like Science and Nature to publish articles and letters by Pascal and others concerning the controversial hypothesis.
In his letters, Hamilton said he was not yet convinced of the vaccine theory, but he warned that the scientific community's failure to give it serious consideration before similar public health campaigns are launched in the future could result in "hundreds of millions of deaths."
Hamilton wrote that he was especially troubled by Koprowski's decision to sue Curtis and Rolling Stone. He compared it to the burning of heretics and the Vatican's 1633 heresy trial of Galileo, calling it an attempt to shut down valid and important scientific discussion.
"Are we starting all over again with a Medical Establishment now in the robes of the universal Roman Church?" he asked.
But Hamilton's concerns were ignored. Both journals declined to publish his letters.
Marx's Question
For Marx, it just didn't add up.
He had left UC Davis and was now conducting research for the Aaron Diamond AIDS Research Center. In his office at the primate center in upstate New York, he grappled with a simple but critical question: If Africans had been hunting and butchering monkeys for hundreds if not thousands of years, routinely exposing themselves to simian viruses, why hadn't an AIDS epidemic erupted earlier?
He was not convinced that the polio vaccine theory was the answer. For one thing, SIV transmitted orally to humans is many times less likely to survive than SIV transferred from monkey blood directly into a human cut.
And evidence now showed that there were actually two AIDS epidemics caused by two distinct viruses - HIV-1 and HIV-2 - that had apparently crossed from different species of monkeys in two regions of Africa that were a thousand miles apart.
Genetic testing by Marx and others showed that HIV-1 appeared to be related to chimpanzees, while HIV-2 was linked to the sooty mangabeys.
Therefore, if the HIV-1 epidemic had been caused by the Wistar vaccine contaminated with a virus linked to chimpanzees from Central Africa, the vaccine could not have caused the HIV-2 epidemic in northern West Africa, where the virus came from sooty mangabeys.
So what caused the two epidemics to suddenly erupt at the same time in the middle of the 20th century, Marx wondered.
The prevailing theory in the scientific community attributed the epidemics to the social upheaval in Africa during the independence struggles of the 1950s and 1960s and the urbanization that followed.
Under that hypothesis, the epidemic emerged as roads were cut through the rain forests and strict colonial travel prohibitions were lifted. This enabled HIV carriers, who had been infected by monkeys and had previously lived in isolated rural communities, to crowd into cities, where they spread the virus through less restrictive sexual practices.
As proof, the theory's advocates pointed to the soaring prevalence of AIDS among African soldiers and prostitutes in cities and along the truck routes criss-crossing Africa.
But Marx was skeptical. Africans had experienced mass displacement and social upheaval before, particularly during centuries of slave trade. By the time slavery was finally abolished in the 1800s, more than 30 million Africans had been uprooted from their tribal homelands. And most of them came from the very areas of Africa where the epidemic would later emerge.
If the virus had been regularly infecting African hunters, even in isolated cases, it likely would have spread to the United States, just as another virus that caused leukemia was spread to America through the slave trade.
Marx's research suggested that something else was at work.
In Sierra Leone he had collected 9,000 human blood samples of which only seven tested positive for HIV. At the same time, more than half the adults in a troop of wild sooty mangabeys he tested were positive for SIV.
It was clear the simian virus only rarely made the jump to humans. And even when the virus did cross the species barrier, Marx found that the people it infected did not become very ill. The virus appeared to cause a "dead-end" infection, so weak that it could not be transmitted sexually to other people.
Yet something had caused this relatively harmless simian virus to turn into HIV, triggering one of the deadliest pandemics in human history.
And Marx thought he might have the answer.
England, 1995
On the morning of March 24, 1995, Hooper picked up a copy of the Independent and on the front page of the London newspaper was the headline: "World's First AIDS Case Was False."
Hooper was stunned.
One of the members of the Wistar panel - acclaimed AIDS researcher Dr. David Ho - had insisted on conducting new tests on the tissue samples from the Manchester sailor.
The new tests found that British seaman David Carr had not died of AIDS, after all. Instead, his tissue samples had apparently been contaminated during earlier laboratory testing with HIV from another patient who died around 1990.
The news meant that the single most compelling piece of evidence undermining the hypothesis that Wistar's polio vaccine had caused the AIDS epidemic had now been eliminated.
The debate about the origin of AIDS was about to heat up.
. Tomorrow: Historic showdown at the Royal Society of London.
The sources used for this series included: Edward Hooper's book, "The River";
the late Chronicle reporter Randy Shilts' seminal work on the beginning of the AIDS
epidemic, "And the Band Played On"; dozens of scientific journal articles by
Preston Marx, Ernest Drucker and other prominent researchers; articles in Atlantic
Monthly, The Village Voice, and Rolling Stone; and news accounts of the Royal Society of
London meeting in September. The series also relied on lengthy interviews with Marx and
Hooper, as well as scores of other interviews with scientists who have been diligently
searching for the genesis of AIDS.
Over the last decade, scientists have discovered that the two viruses responsible for the global AIDS epidemic, HIV-1 and HIV-2, came from simian viruses that jumped the species barrier to humans from two different kinds of African monkeys.
HIV-1, which has caused the vast majority of worldwide AIDS cases, came from chimpanzees that live in either Central or West Central Africa. HIV-2, which infects people located primarily in West Africa, has been traced to a virus found in the sooty mangabey monkey, which lives in a coastal range in West Africa.
In 1999, former BBC radio reporter Edward Hooper published a book called "The River" in which he contends the AIDS epidemic was caused by a contaminated polio vaccine that was given to hundreds of thousands of people in Central Africa in the 1950s. His theory, which some have called flawed, cites the strong correlation between the rural African clinics where the Wistar oral vaccine was administered from 1957 to 1960 and the villages where the earliest AIDS cases turned up. . -- Preston Marx travels to Liberia in 1988 to find the sooty mangabeys believed to be the source of HIV-2. . -- Researchers argue over which subspecies of chimpanzees was the source of HIV-1. Hooper believes the virus may have come from chimpanzee subspecies in Central Africa. Others contend that the virus came only from "pan troglodytes troglodytes" chimpanzees from West Central Africa. . -- Edward Hooper visits Kasenero, Uganda, in 1986 and learns that 100 villagers have died of "slim" disease, their name for AIDS. That encounter began his search for the origin of the epidemic.
THE PROCESS WISTAR USED TO MAKE ORAL (live) POLIO VACCINE . (1) A pure strain of poliovirus is isolated. (2) The poliovirus is grown in a series of monkey kidney-tissue cultures until it is incapable of causing sickness. (3) The weakened strain is tested on chimpanzees to ensure that it is safe and effective. (4) The live, but weakened "seed" virus is then grown in large quantities in fluid form over a single layer of monkey kidney tissue to produce the vaccine. (It is at this stage in the process that Hooper contends the Wistar polio vaccine may have contaminated with a simian virus. Wistar categorically denies the allegation.) (5) The final vaccine is administered orally to humans, triggering the immune system to destroy any natural polio infection. . Sources: The River by Edward Hooper; National Geographic; Poliovirus image courtesy Jean-Yves Sgro and University of Wisconsin .
Email William Carlsen at wcarlsen@sfchronicle.com.