Did Modern Medicine Spread an Epidemic?
After decades, and millions of injections, scientists are asking the chilling question
http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2001/01/15/MN162301.DTL

Quest for the Origin of AIDS
Rogue virus in the vaccine

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.

Hooper's Theory

London, 1997

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.

The Wrong Chimpanzees

Birmingham, Alabama, 1999

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.

Hamilton's Foreword

London, 1999

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 ŒThe 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.

Millions of Injections

New York, 1999

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.

The Rain Forest

Central Africa, January 2000

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 Eve Virus

San Francisco, February 2000

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.

Another Casualty

London, March 2000

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 Trial

London, September 2000

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.

The Smoking Guns

London, 2000

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.

Deadly Needles

London, 2000

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 transmissable.

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.

The Search's Value

Birmingham, Alabama, October 2000

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.

Marx's Plan

Cameroon, October 2000

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 Presses On

Bridgwater,England,

January 2001

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."

And recent articles in science journals have also been encouraging, he said, including the article by two Danish geneticists that raised questions about the molecular dating of HIV-1.

Hooper believes the Royal Society meeting was stacked against him. "I lost the public relations battle at the Royal Society,'' Hooper said. "But there is still a great deal to be discovered, and the debate is not over.''

Sources for This Series

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.

Tracing HIV to Its Simian Source

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. .

Locating the Origin of HIV

Camp Lindi

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.

Needle Influx

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.

E-mail William Carlsen at wcarlsen@sfchronicle.com.