San Francisco Chronicle, Sunday, 14 January 2001, pp. A1, A14-A15
(First of a two-part series)
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.
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.
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.
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.
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 for decades 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.
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.
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 transmissibility 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 HIV.
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.
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.
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 Philadelphia. During the 1950s, Koprowski, a Polish Emailer 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 Wistar 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.
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 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.
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.
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 of 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.
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.
San Francisco Chronicle, Monday, 15 January 2001, p. A11
(Last of a two-part series)
The two men met purely by chance.
On an October 1997 flight from New York City to New Orleans, virologist Preston Marx noticed the passenger in the aisle seat was reading an article about one of his colleagues at an AIDS research center in Manhattan.
The passenger, Ernest Drucker, was a professor at New York's Albert Einstein College of Medicine, and he told Marx he had been studying the role of unsterile needles in the upsurge of AIDS among heroin users in Asia, South America and West Africa.
Marx was captivated. For years he had been searching for the origin of the AIDS epidemic. He was a primate researcher who had been one of the first to trace a virus in monkeys that was remarkably similar to HIV. Later, during field trips to West Africa, Marx had become convinced the simian virus had been crossing the species barrier to humans for centuries.
But for the past few years he had been trying to figure out why the AIDS epidemic had only erupted in the middle of the 20th century.
As the flight to New Orleans wore on, Marx and Drucker began to talk about the injection campaigns that had rolled through Africa during the 1950s, a period of swashbuckling medical optimism when the World Health Organization and other relief agencies launched massive programs to eradicate disease.
The two men knew that the reuse of needles during those campaigns certainly could have spread HIV from patient to patient. But could the contaminated needles themselves actually have transformed the relatively harmless simian virus into a deadly killer that has claimed the lives of more than 20 million people?
It was a terrible question because it raised the chilling possibility that one of the most devastating epidemics in history had been inadvertently caused by an intervention of modern medicine.
But Marx and Drucker were not the only ones to raise that question - and the hypothesis they would eventually develop would never be as controversial as a rival theory being advanced by a former BBC reporter named Edward Hooper.
For seven years, Hooper had researched a book about the genesis of AIDS. He reviewed thousands of pages of medical records, scientific papers and government documents, and he conducted more than 600 interviews in Africa, Europe and the United States.
A literature major in college, Hooper taught himself molecular biology, virology, geography, primatology and other disciplines. He analyzed virtually every plausible theory about the origin of the AIDS epidemic.
And the more he learned, the more he came to believe the AIDS epidemic had been caused by an oral polio vaccine given to hundreds of thousands of people in Central Africa in the late 1950s.
The vaccine had been developed by acclaimed virologist Hilary Koprowski, director of the Wistar Institute of Philadelphia, and Hooper believed monkey kidney tissue used to grow the vaccine may have been contaminated with a simian virus genetically related to HIV.
During his research, Hooper learned that in the 1950s approximately 400 captured chimpanzees had been used for polio research at Wistar's Camp Lindi near Stanleyville (present-day Kisangani in Democratic Republic of the Congo).
Koprowski and other Wistar officials insisted the chimpanzees at Camp Lindi were used only to test the safety and efficacy of the vaccine. They said the polio vaccine was produced in kidney tissue taken from Asian macaque monkeys only - not chimpanzees.
But Hooper found evidence that some Camp Lindi chimpanzees were killed and their kidneys sent to the Wistar laboratories in Philadelphia and possibly Belgium, where the vaccines used in Africa were apparently made.
From records and interviews, Hooper located the rural villages where the Wistar vaccine had been administered between 1957 and 1960 in former Belgian colonies now called the Democratic Republic of the Congo, Rwanda and Burundi. Then he screened the records of HIV-positive blood samples collected in Africa before 1981.
He found that 47 of the 52 HIV-positive blood samples came from villages where the Wistar vaccine was administered. And all the samples were taken within 100 miles of vaccination sites, including several not far from the Ugandan village along Lake Victoria where a decade earlier dying villagers first told him about a mysterious disease they called "slim."
It was compelling circumstantial evidence for a theory that Hooper knew the scientific community didn't want to hear. For years some of the world's leading science journals had declined to publish articles - or even letters - that discussed it.
But as far as Hooper was concerned, he had made a case that could no longer be ignored. And in late 1997, he plunged into writing the book's final draft.
For months, Dr. Beatrice Hahn and her colleagues at the University of Alabama carefully studied the viruses they found in blood samples taken from four chimpanzees.
Three of the chimpanzees were from a subspecies (Pan troglodytes troglodytes) found in the West African nations of Cameroon and Gabon. The fourth was from another subspecies (Pan troglodytes schweinfurthi) found more than 700 miles away - in the Central African region that had produced chimpanzees for the Wistar Institute's Camp Lindi in the 1950s.
By analyzing the SIV's genetic code, Hahn's team discovered that the viruses in the three West African chimpanzees were clearly related to HIV-1, the virus responsible for most of the global AIDS epidemic. But the SIV found in the fourth chimpanzee had noticeably fewer genetic similarities to HIV-1.
Their findings, published in Nature, provided the closest link so far between HIV-1 and what they claimed was probably its primate source - West African chimpanzees.
And because chimpanzee subspecies rarely range far from their indigenous habitat - they are notorious for their aversion to crossing even small rivers -
Hahn's findings cast doubt on Hooper's theory that viruses from the Central African chimpanzees at Camp Lindi had contaminated the Wistar vaccine and ignited the HIV-1 epidemic.
Before his book came out, Hooper turned to Oxford Professor William Hamilton to write the foreword.
He could not have found a more respected voice. The evolutionary biologist was one of the most distinguished scientists in the world and had been an early supporter of Hooper's work.
Hamilton was deeply impressed with Hooper's research, even though he recognized that Hooper had not conclusively proved the Wistar vaccine had caused the AIDS epidemic.
In his book, Hooper had not only presented a significant body of indirect evidence in support of the contaminated vaccine theory, he had also analyzed the strengths and weaknesses of virtually every other theory or avenue of research attempting to explain how the AIDS epidemic started. It was a carefully researched and exhaustive undertaking, particularly for a nonscientist.
"The new facts in the case still tend to be widely separated and none by itself amounts to proof," Hamilton wrote. "However, if taken together the steady trend and accumulation has become very impressive."
At the very least, Hamilton believed, Hooper's research and the questions it raised deserved serious consideration, and Hamilton warned the scientific community of the dangers in failing to do so.
"The thesis of 'The River' is that the closing of ranks against inquiry may, in this case, be preventing proper discussion of an accident that is bidding to prove itself more expensive in human lives than all the human attritions put in motion by Hitler, Stalin and Pol Pot."
Hooper's "The River: A Journey to the Source of HIV and AIDS," was published in August 1999. It is 1,070 pages long. The footnotes alone take up 175 pages.
The book drew widespread media attention. The Los Angeles Times called it "a cautionary tale for researchers." The London Review of Books said Hooper "may or may not have found the source (of AIDS) but he certainly has written a gripping mystery story." The British medical journal, The Lancet, suggested that "perhaps (scientific) opinion will shift once the book has been read."
But reaction to "The River" was far more strident in Africa, where the book prompted calls for reparations and civil suits against individuals and institutions involved in the 1950s vaccine trials.
"If it turns out that the real cause of the current pandemic was bad science, albeit in pursuit of noble goals," wrote the East African, "should not Africa's leaders . . . pursue the matter relentlessly using all legal and forensic resources available?"
Hamilton, a member of Britain's respected science academy, the Royal Society, decided the time had come for a full scientific discussion on the origin of AIDS.
So in late 1999, he began arranging for the first-ever international conference on the subject in London, where Hooper and "The River" would finally have their day.
As Marx pressed ahead with his field work in West Africa, Drucker was gathering data from the World Health Organization, needle manufacturers and drug companies.
Drucker found that shortly after World War II the sudden availability of penicillin and other antibiotics had created a huge global demand for syringes.
At the same time, the cost of syringes plunged as manufacturers switched from glass to inexpensive plastic syringes, and production jumped 100-fold in a single decade.
Armed with the new drugs and millions of the inexpensive needles, the United Nations launched a series of campaigns to combat malaria, syphilis and other illnesses. Between 1952 and 1957, international relief agencies administered 12 million injections of penicillin in Central Africa alone.
The campaigns were a medical intervention on a scale never seen before on the African continent. But the noble goal of eradicating disease was compromised by a widespread failure to ensure sterile injections, and the consequences of that failure could be staggering.
In the 1960s, Drucker learned, health officials in Egypt had waged a mass-injection campaign to treat an illness called schistosomiasis. One result of the campaign was a massive outbreak of hepatitis C, spread through the reuse of contaminated needles.
If hepatitis C virus could be spread through the reuse of needles, so could HIV. But Marx and Drucker were becoming increasingly convinced that needles were doing more than simply spreading the disease.
In January, Hamilton and two assistants traveled to the dense equatorial rain forest of the Democratic Republic of the Congo, hoping to collect fecal and urine samples from chimpanzees that lived near Camp Lindi to see if they contained viruses similar to HIV-1.
Hamilton and Hooper were not convinced that chimpanzees from West Central Africa were the only source of HIV-1, as Hahn had suggested. For one thing, Hahn had based her findings on the test of a single chimpanzee thought to have come from the Camp Lindi region.
And Hooper had discovered that Camp Lindi also kept a colony of about 80 pygmy chimpanzees, a rare subspecies (Pan paniscus) from the area that also might harbor a virus genetically similar to HIV-1.
The problem was that the area around the former camp near Kisangani was in the throes of civil war. On a collecting trip seven months earlier, Hamilton had been stopped and threatened by soldiers.
But he was determined to return to the Central African rain forest to test Hooper's thesis, and he worried that they might not have a lot of time. The chimpanzees in the area were quickly being killed for food by people starving because of the civil war.
The soft-spoken geneticist from Los Alamos National Laboratory had some startling news.
Speaking at the 7th annual Conference on Retroviruses and Opportunistic Infections held at San Francisco's Marriott Hotel, Bette Korber announced that she and her colleagues had used Nirvana, the world's most powerful supercomputer, to trace the origin of HIV-1 to 1930, although the exact date could fall between 1910 and 1950.
At the New Mexico facility, Korber and her team had focused on HIV-1, Group M, the deadliest strain of the virus and the one that has infected more than 50 million people worldwide and left more than 20 million dead.
As the Group M strain spread through Africa and around the world, it had mutated, branching out to form 11 viral subtypes, according to Korber. By unwinding the genetic clock and tracing those branches back to the HIV-1 trunk,
Korber's team said it was able to estimate the date of the last common ancestor or "Eve" Group M virus.
The team said it confirmed its calculations by comparing their estimated evolutionary history of the virus with the scattered dates of the earliest known AIDS cases - the famous ZR59 blood sample taken near Leopoldville in 1959 and samples collected from 159 other HIV-infected individuals.
Korber acknowledged her calculations could not prove when the virus actually jumped from chimpanzees to humans. The 11 viral subtypes could have branched out in chimpanzees or humans, she told the conference.
But her research was yet another blow to Hooper's contaminated vaccine theory, because it meant all 11 subtypes would have had to have been transferred from chimpanzee kidneys to humans by the Wistar vaccine - a possibility that Korber called "highly unlikely."
It was more likely, Korber said, that the ancestral virus crossed from a chimpanzee to a "founder" human at some point before 1930, then began mutating into its various branches as it was transmitted to other humans - decades before the Wistar vaccine trials took place.
After collecting dozens of chimpanzee samples in the northeast region Democratic Republic of the Congo, Hamilton returned to Kisangani in late January.
A few days later, he began feeling ill. He had decided not to take anti-malarial pills in Africa because he had contracted the disease in the Amazon years before and he believed the antibodies in his immune system would protect him.
He was wrong. In Kisangani, he was bedridden with fever and the sweats. He was briefly hospitalized in Uganda and was given pain pills.
Then he returned to London, where he collapsed and was hospitalized with a massive internal hemorrhage. Apparently, Hamilton's body had fought off the malaria, but the pain medication had ruptured a blood vessel. A short time later, he sank into a coma.
In early March, at the age of 63, William Hamilton died. The AIDS epidemic had claimed another victim.
The Royal Society conference that had been initiated by Hamilton was called "Origins of HIV and the AIDS Epidemic," but some in the media billed it as nothing less than modern medicine on trial.
In early September, some of the most prominent AIDS researchers in the world flew into London for the two-day conference - and one by one they presented findings that contradicted the central thesis of "The River."
Hahn explained how she and her team had isolated the probable precursor virus to HIV-1 in chimpanzees in West Africa - far from Camp Lindi and the Wistar vaccine experiments.
Korber described the dating of the "Eve virus," which she had recently revised to 1931 (with a range of 1915 to 1941) - years before Koprowski began administering his oral polio vaccine to hundreds of thousands of Central Africans.
John Beale, a pharmaceutical and vaccine expert, explained that the Wistar vaccine was produced using heat treatment, as well as cycles of freezing and drying, that would kill most viruses. The vaccine was also made with an enzyme that strips the protein covering from viruses, rendering them harmless. Beale estimated that only one viral particle in 10,000 billion could survive the process.
Others observed that the different strains of HIV-1 and HIV-2 suggested the simian viruses had crossed the species barrier more than once, undermining the likelihood that the AIDS epidemic began with a single virus crossing to humans in the Wistar vaccine.
And finally, Dr. Claudio Basilico of New York University Medical Center announced that samples of the seven remaining batches of the Wistar vaccine, including pools 13 and 10a-11, the most likely used in Africa, were analyzed in independent laboratories in the United States, France and Germany. The testing found no evidence of SIV or DNA from chimpanzees.
In the aggregate, the research raised grave - and perhaps insurmountable - concerns about the contaminated vaccine theory.
But Hooper, unfazed, rose to defend the theory that had dominated the past eight years of his life.
He told the researchers that because of the civil war raging in the Congo not enough samples had been gathered to rule out the possibility that HIV-1 had originated with the Camp Lindi chimpanzees.
He disputed Korber's suggestion that the "Eve virus" for HIV-1 most likely crossed the species barrier before 1931. He insisted it was possible the viral subtypes could have evolved in chimpanzees and crossed to humans in the Wistar vaccine.
He said despite Beale's assertion that the virus was unlikely to have survived Wistar's production process, there was evidence that at least one simian virus had survived an oral vaccine-making process.
And he summarily dismissed the laboratory analyses that found no evidence of SIV or chimpanzee DNA in the Wistar vaccine, saying that "none of the Wistar samples which have just been tested were prepared for use in Africa."
And that wasn't all.
Since "The River" was published, Hooper told the scientists, he had also uncovered two new "smoking guns" in Africa, both of them supporting the contaminated vaccine theory.
Hooper said he recently interviewed a veterinarian from Camp Lindi who claimed that two doctors working in the camp in the 1950s told him chimpanzee kidneys were sent to the United States at Koprowski's request.
Hooper said he also interviewed a man who had worked in a lab in the former Belgian colony (present-day Burundi) who told him chimpanzee kidneys in the 1950s were routinely sent to a medical lab in the nearby city of Butare.
There, Hooper said, he found records showing the lab had been involved in vaccine production. For the first time, he said, there was evidence suggesting small batches of Koprowski's vaccine may have been made in Africa itself, using chimpanzee kidneys.
Noting that Butare was a site where the Wistar vaccine had been administered, Hooper said 29 out of 33 prostitutes there tested positive for HIV-1 in 1984, "an extraordinary percentage for so early in the AIDS epidemic."
Hooper adamantly refused to admit the vaccine theory had been discredited. But he tried to end on a conciliatory note.
"This debate is not about blame or culpability," he said. "(Wistar's) research in Africa, though highly secretive, was carried out for a noble end."
He urged the doctors who developed the vaccine to disclose everything.
But Stanley Plotkin, a Wistar official who helped administer the vaccine in Africa, delivered a blistering rebuttal. Plotkin said he had written statements from the 16 members of the team that had developed the vaccine and all of them denied any chimpanzee tissue had been used.
Plotkin also attacked as faulty Hooper's correlation of the earliest AIDS cases with the sites where the vaccine was administered, and he noted the vaccine tested in the Congo had also been administered in Poland and the United States, yet no outbreaks of AIDS cases resulted there.
He told the conference that Hooper's theory was completely baseless. There is, he said, "no gun, no bullet, there is no shooter, there is no motive. There is only smoke created by Mr. Hooper."
Finally, Koprowski himself, now in his 80s, rose to defend his life's work.
In the 1960s, Koprowski had lost the race with Albert Sabin to license an oral polio vaccine, but his pioneering work had played a critical role in the development of a cheap, easily administered vaccine.
"My achievement of developing oral polio vaccines saved millions of lives," he told the scientists. "But now I am held up before the world as the father of AIDS - a mass murderer."
Koprowski categorically rejected Hooper's theory, charging that Hooper "operated with preconceptions without much attention to contradictory data."
Modern medicine and science were not responsible for the AIDS epidemic, Koprowski said, but now Hooper's book could be blamed for undermining the final global effort to eradicate polio.
In Kenya, Koprowski said, Roman Catholic clerics, afraid that polio vaccines are contaminated with HIV, are advising parents not to vaccinate their children.
In the middle of the furor, Marx and Drucker quietly waited their turn.
Finally, near the end of the conference, Marx took the podium and presented their theory to the assembled researchers.
He told the conference he and Drucker believed the mass injection campaigns in Africa during the 1950s not only helped spread the AIDS virus but the widespread reuse of contaminated needles actually caused the harmless simian viruses - which usually caused weak, dead-end infections in humans - to become deadly and transmissible.
The lethal transformation occurred through a process called "serial passage, " Marx said.
That process occurs when patient A - infected with a simian virus through a splash of monkey blood in an open cut - receives an injection. When the same needle, carrying patient A's contaminated blood, is reused, the virus is transmitted to patient B.
That sequence is then repeated when the virus from patient B is transmitted to patient C by another unsterile needle, and so on.
In each patient, Marx explained, the virus rapidly adapts to its host's immune system through mutations, growing stronger before it is passed to the next patient. Through that process, the virus grows increasingly virulent until it is not only lethal but can be easily transmitted through sexual activity. The SIV has been transformed into HIV.
The process had already been witnessed in monkey experiments, Marx told his colleagues. Simian viruses became 1,000 times more pathogenic as they were "serially passaged" through as few as three monkeys.
Marx acknowledged that the serial passage of a virus in humans would be a very rare occurrence. But the huge influx of needles in Africa, particularly in the 1950s, exponentially increased the opportunity for serial passage to occur, he said.
And if the those injection campaigns had caused the virus to turn deadly, the responsibility for the AIDS epidemic rests not with a contaminated vaccine but with a different intervention of modern medicine - the introduction of the hypodermic needle.
"The consequences of massive unsterile injecting appears to be another case of unintended consequences of technological innovation," Marx said.
And he warned that if needles continue to be reused in Africa and elsewhere, new strains of viruses may cross the species barrier to humans and ignite new epidemics.
In her laboratory at the University of Alabama, Hahn is preparing to analyze some of the chimpanzee fecal and urine samples Hamilton collected in Central Africa before his death.
But she believes that no matter what the testing finds, Hooper's vaccine theory was largely discredited at the Royal Society meeting.
"But he has done a great service," she said. "He has galvanized the field and refocused research on the subject."
Hahn, who studied under Robert Gallo, one of the co-discoverers of HIV, also has reservations about Marx and Drucker's theory. The timing is off, she said, because the 1950s mass injection campaigns came decades after HIV probably first appeared in humans.
She knows that Marx, a longtime friend and collaborator, is working with Drucker and others to address that question and others. And recent scientific publications have raised questions about the 1931 genetic dating of HIV-1, Group M, by Korber.
Hahn says it is is entirely possible that scientists may never find the precise origin of the AIDS epidemic.
Still, she said, the search must continue.
"Many people ask me why we poke around in the past. The answer is that what we have learned of AIDS history during the last decade is extremely important."
Each new discovery, she explained, moves science toward an understanding of how viruses cross the species barrier and how we might head off epidemics like AIDS in the future.
In October, Marx flew into the humid port town of Douala on the coast of Cameroon.
Reaction to the contaminated needles theory Marx and Drucker presented at the Royal Society conference in London had been good.
Conference chair Robin Weiss of the University College of London told New Scientist magazine: "It has the ring of truth about it."
Tom Burr, a statistician from Los Alamos National Laboratory, said the needle theory fits with a recent computer study indicating that some event seemed to have occurred in the "narrow time frame" of the 1950s or 1960s that may have resulted in the burst of HIV subtypes.
"Needles works" to explain those findings, Burr said, adding that Hooper's polio vaccine theory did too.
And both Marx and Drucker have prepared papers about their hypothesis for several scientific publications, including The Lancet.
In Douala, Marx was picked up by one of his field assistants in the group's air-conditioned Land Cruiser. Instead of heading south through the dense coastal rain forests to one of his group's field research stations, he turned inland and made his way to Yaounde, Cameroon's capital city.
There he met with government officials, and presented them with a new plan to test his theory. He would collect used needles from Cameroon's medical clinics, providing them with new needles in exchange.
Then back in the United States, he and another researcher from Yale will analyze the viruses they find in the dried blood on the used needles.
From the samples, they hope to capture the different stages of SIV as it "serially passages" into HIV.
"We're going to try and catch the virus in the act," he said. "It's a long shot, and it will take some time, but it's worth a try."
Hooper refuses to give up.
He is convinced that nothing at the Royal Society conference conclusively disproved the contaminated vaccine theory, and he continues to collect more evidence to support it.
"As we speak," he said in a interview last week, "new gathering expeditions in Africa (for chimpanzee fecal and urine samples) are underway. Virtually no chimps have been sampled and that must be done."
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 origin of AIDS.
The worldwide AIDS epidemic is caused by two distinct viruses, HIV-1 and HIV-2,that experts believe crossed the species barrier to humans from two different species of African monkeys.
SIV: Simian Immunodeficiency Virus Researchers first isolate SIV in 1985 after the virus infects and kills Asian monkeys in U.S. research labs. It is traced to the sooty mangabey monkey, an African species that is immune to the virus but can infect other monkeys. In the late 1980s, researchers discover that SIV and HIV are genetically related.
HIV-1: The Global Virus HIV-1 is linked to an SIV found in chimpanzees.
Experts believe that the Group M strain of the virus came from a single transmission from chimp to human in the early to mid-20th century. Since then, the virus spread around the world branching into 11 viral subtypes. Subtype B of Group M is commonly found in the United States. Group N and Group O strains of HIV-1 came from separate chimp to human transmissions and have resulted in a limited number AIDS cases primarily in Africa.
HIV-2: A Separate Virus
HIV-2 is linked to SIV found in sooty mangabeys. Researchers believe that there are two main subtypes from two separate transmissions from mangabeys to humans. The virus is less infective and it takes a longer period before AIDS appears. The epidemic is found primarily in West Africa.
In the 1950s, the Wistar Institute built Camp Lindi in the Congo, where 400 chimpanzees were kept for polio vaccine research. In his book, "The River," Edward Hooper contends that kidneys infected with SIV were removed from the chimpanzees and used to make the oral vaccine, contaminating it and starting the AIDS epidemic. Wistar categorically denies the allegations.
A recent theory by Preston Marx contends that the AIDS epidemic started with the reuse of contaminated needles during disease eradication campaigns in the 1950s in West and Central Africa. The needles turned a harmless monkey virus into HIV through a process called serial passage.
The Theory of Serial Passage with Contaminated Needles
1. Market woman is infected with SIV when she butchers a sooty mangabey during food preparation. She then receives an injection.
2. The same needle is used on a second person. The SIV from the woman infects the second person. The second person returns for another injection with a new needle.
3. That same needle is reused and the virus infects a third person. The SIV has begun to adapt to the human immune system and grows stronger. The third person receives another injection with a new needle.
4. That same needle is used on a fourth person. The SIV adapts and grows stronger. That person returns for another injection.
5. The virus continues to "passage" through several more persons traveling between them on reused needles. Eventually, the SIV has been transformed into HIV and is virulent enough to be passed on through sexual contact -- ready to start an epidemic.
John Blanchard / The Chronicle
KEY DEVELOPMENTS IN THE QUEST TO FIND THE ORIGIN OF THE AIDS EPIDEMIC SMALLPOX: Between 1893 and 1912, vaccination campaigns to combat smallpox roll across Africa.
SLEEPING SICKNESS: Mass vaccinations to combat sleeping sickness are carried out in West and Central Africa. But during those campaigns, needles are reused repeatedly. From 1917 to 1919, for example, only six syringes are used to vaccinate up to 90,000 people in present-day Central African Republic.
PENICILLIN: Production of the powerful antibiotic penicillin dramatically increases following World War II. Between 1943 and 1949, penicillin production rose from 21 million to 120 million units.
DISPOSABLE SYRINGES: Glass syringes begin to be replaced by inexpensive plastic disposable syringes. Between 1950 and 1960, the number of syringes skyrockets to 1 billion units.
YAWS CAMPAIGN: Between 1952 and 1957, UNICEF's campaign to eradicate a disease called yaws results in 12 million injections of penicillin in Central Africa.
WISTAR TRIALS: Between 1955 and 1960, the Philadelphia-based Wistar Institute administers an experimental oral polio vaccine developed by Hilary Koprowski to hundreds of thousands of people in Central Africa.
THE MAN FROM LEOPOLDVILLE: Blood from a Congo man is collected in 1959 near Leopoldville (present-day Kinshasa) and then is taken with other samples to the University of Washington in Seattle. In 1986, the sample is retested and shows antibodies for HIV. The sample represents the earliest evidence of human infection with the AIDS virus.
OMINOUS SYMPTOMS: In 1975 the first reports of symptoms, later determined to be AIDS, are reported in residents of Africa.
GAY VICTIMS: Beginning in 1981, gay men in Los Angeles, New York, San Francisco and elsewhere begin dying from AIDS.
THE VIRUS: Researchers isolate the human immunodeficiency virus (HIV) in 1984.
A SECOND VIRUS: For more than a decade, Asian monkeys were mysteriously dying in primate research centers in the United States, exhibiting many AIDS- like symptoms. In 1985 researchers isolate the simian immunodeficiency virus (SIV).
THEORY EMERGES: In 1987, a nonscientist from New York City named Louis Pascal writes a paper that for the first time argues that the HIV epidemic was caused by a contaminated oral polio campaign in Central Africa in the late 1950s. He contends that the monkey tissue used to culture the vaccine contained SIV. Pascal submits the paper to numerous scientific journals, but four years pass before it is finally published by an Australian university.
THE LINK: Researchers genetically link SIV to HIV in 1988.
TWO DISEASES: In 1989 researchers discover that SIV carried by chimpanzees appears to be linked genetically to HIV-1, and a second SIV carried by sooty mangabey monkeys is linked genetically to HIV-2, a separate and distinct AIDS virus.
HOOPER'S QUEST: In 1990, four years after visiting a small fishing village on the shore of Lake Victoria, where dozens of villagers were dying of a disease they called "Slim," former BBC correspondent Edward Hooper (pictured at right) begins intensive research into the origin of the AIDS epidemic. His research culminates in the publication of "The River" in 1999.
SPECIES BARRIER: Virologist Preston Marx publishes a paper in 1991 in which he suggests that SIV had been crossing the species barrier from sooty mangabey monkeys to humans, who hunted, butchered and ate the mangabeys, as well as kept the orphans for pets.
ROLLING STONE: Freelance science writer Tom Curtis publishes an article in Rolling Stone magazine in March 1992, suggesting that the Wistar polio vaccine administered in Africa in the late 1950s may have passed SIV to humans, triggering the HIV epidemic. It is essentially the same theory advanced by Pascal five years earlier.
WISTAR'S DEFENSE: Following the publication of the Rolling Stone article, the Wistar Institute convenes a panel of independent experts who produce an October 1992 report that rejects the central allegations of the article, calling it very unlikely that the oral polio vaccine transmitted SIV to humans.
CLARIFICATION: In 1993, Rolling Stone prints a clarification to the Curtis article, saying it never intended to suggest there was evidence showing that the Wistar vaccine caused the AIDS epidemic.
NEEDLE THEORY: Marx and AIDS researcher Ernest Drucker theorize in 1997 that widespread reuse of contaminated needles during disease eradication campaigns in Africa in the 1950s may have caused the AIDS epidemic.
SERIAL PASSAGE: In 1998, laboratory studies show that a nonpathogenic SIV-like virus passed by needles through three monkeys created adaptive mutations in the virus that allowed it to become pathogenic and virulent.
CHIMPANZEES: University of Alabama researcher Beatrice Hahn and colleagues report in 1999 that the most likely source of HIV-1 is a subspecies of chimpanzees found in West Central Africa, not in the Congo area where the polio vaccine was developed.
"THE RIVER": Hooper's 1,070-page book is published in 1999 laying out circumstantial evidence that the Wistar polio vaccine caused the AIDS epidemic.
EVE VIRUS: January, 2000, Bette Korber, a scientist at the Los Alamos National Laboratory in New Mexico, and her colleagues determine that the common ancestor of the various subtypes of HIV originated in approximately 1930, more than two decades before the Wistar vaccine was given to Central Africans.
ROYAL SOCIETY: On Sept. 11 and 12, the Royal Society of London holds the first major conference on the origin of AIDS, assembling medical experts including Hooper, Koprowski, Korber, Hahn, Marx and Drucker. Hooper's theory comes under intense scrutiny, and Marx and Drucker announce that they now believe the reuse of contaminated needles not only spread the AIDS virus but triggered the mutation of SIV to HIV in humans.