Something Happened

1.

In the movie version of H.G. Wells's The Island of Dr. Moreau, a shipwrecked passenger is fished out of the sea by a cargo ship on its way to deliver crates of apes, lions, and other wild animals to a reclusive and mysterious scientist on an island in the South Pacific. At one point the passenger asks a member of the ship's crew, "Hey, what is all this mystery about Moreau and his island?" "I don't know," says the sailor. "If I did know, maybe I'd want to forget."

Dr. Moreau is tinkering with evolution. He has moved to this remote island laboratory to create a hybrid race of beast-men. He wants to change "the physiology, the chemical rhythm" of these creatures, something similar, he says, to vaccination. Moreau believes he is working in the service of mankind and science, but in the end his beast-men turn on him and destroy his laboratory and everything else on the island. Reading The River, Edward Hooper's book about the origin of the AIDS epidemic, I began to wonder whether Hooper had ever read Wells's book or seen Island of Lost Souls. I also wondered just how prescient Wells might have been about what goes on in modern biology labs. "The spirit of Dr. Moreau is alive and well and living in these United States," says the science-fiction writer Brian Aldiss in the afterword to a recent edition of Wells's book. "These days, he would be state funded."

Thirty-three million people living in the world today carry HIV. So far fourteen million have died of AIDS. In some urban areas in Botswana, Zimbabwe, and Malawi more than 20 percent of sexually active adults are infected with HIV. The UN estimates that AIDS is responsible for 5,500 funerals a day in Africa. The disease is ruining families, villages, businesses, and armies and leaving behind a sadness so immense that it may take hundreds of years to heal.

AIDS is caused by a family of viruses called HIV that destroy the immune system that protects the body from disease. These viruses pass from person to person in bodily secretions during vaginal, anal, or oral sex; they also pass through blood transfusions and pharmaceuticals made from blood products and through bloody hypodermic needles. Infected mothers may also transmit these viruses to their babies in the womb or through breast-feeding. There is no cure, and the immune defenses of even the lucky patients who can afford the newest, most expensive treatments eventually falter. Death, often painful, follows diseases caused by strange microbes that once were extremely rare.

Some African monkeys and apes carry viruses that closely resemble HIV, and most AIDS researchers now believe that the HIV viruses are really primate viruses that somehow jumped into human beings. HIV-1, the virus responsible for most cases of AIDS to date, probably came from a chimpanzee, and HIV-2, a less aggressive virus more common among West Africans, almost certainly came from a monkey called the sooty mangabey.

In thousands of years of human history, not a single person is known to have been infected with HIV until 1959. It is possible that there were cases before that year, but no colonial medical officer, African doctor, or traditional healer ever noticed them. Now 16,000 people become infected with HIV every day and 7,000 people die of AIDS. Why have these horrible viruses started killing people in such vast numbers now and never before? Numerous explanations have been proposed. AIDS has been said to be a divine act, punishing humanity for its godless ways. Or the viruses were allegedly concocted in germ warfare labs in Maryland or the USSR or at the UN and then escaped. It has even been claimed that they came from outer space. Hooper has devoted more than a decade to this question, and he does not seem to know for certain why HIV turned up now and never before. His best guess, however, is that HIV emerged from an accident in a jungle laboratory in the 1950s, not all that much unlike Dr. Moreau's.

In the 1950s, a group of scientists associated with the American pharmaceutical company Lederle, and later the Wistar Institute in Philadelphia, were racing to develop the first polio vaccine that could be given by mouth instead of by injection. Hilary Koprowski, a Polish-American vaccine expert, was the leader of this team.

Oral polio vaccines are now one of the greatest successes of modern science. They are administered throughout the world, and the World Health Organization predicts that early in the next century an extensive international vaccination campaign will have eradicated polio from all the world's populations. The vaccines used are those of Albert Sabin, who eventually won the race against Koprowski, but the two teams were very close for some time.

Back in the 1950s, Koprowski was impatient to test his vaccine on a large number of people, and since he had contacts with doctors in the Belgian Congo he decided to launch a vaccine trial there. The Belgian authorities were obliging, and in those days this approval was all that was required. Over a period of three years, between 1957 and 1960, Koprowski and his colleagues fed his oral polio vaccine to approximately one million Africans in Congo, Rwanda, and Burundi.

Although this was a trial, the African subjects were not aware of it. All they knew was that their local chiefs had summoned them to line up before a group of white doctors who were dispensing what they were told were "sweets" but which were actually mouthfuls of vaccine squirted from a metal syringe. Koprowski and his Belgian colleagues kept a colony of a few hundred chimps at a research station in a remote part of the Congo beside the Lindi River. They used these chimps in experiments to test the safety and effectiveness of the polio vaccines. However, Hooper believes the vaccines used in Koprowski's African trials were contaminated with the primate precursor of HIV, and that it came from the chimpanzees at Lindi.

Oral polio vaccines are polio viruses that have been weakened so that they don't cause disease. In the Fifties, scientists grew live polio vaccines in monkey kidneys that had been cut into tiny pieces and placed in a jar filled with fluid. Cells would grow out of the minced pieces of tissue and form a sort of underwater floor on the bottom of the dish. A few drops of a solution containing a weak vaccine strain of polio virus would be added to the dish; the virus would reproduce inside the cells, and after a week or so the fluid would be teeming with living polio vaccine virus. The fluid was filtered, diluted, and then fed to people. Their immune systems would learn to kill the vaccine virus, and when vaccinated people encountered the real virus later on, their bodies would be able to fight it off.

Hooper believes that Koprowski sent the kidneys of some chimpanzees from his Lindi research station to his lab in Philadelphia and used them to make the vaccine that was later administered in Africa. In The River Hooper painstakingly tries to account for every chimp that was ever kept at Lindi in the late 1950s. He found that many died shortly after they were captured, and many others were killed after being used in experiments, but he claims that the fate of a few dozen chimps went unrecorded. If, as Hooper believes, the kidneys of these missing chimps were actually used to make Koprowski's vaccine, then it is possible that this vaccine might have contained the chimp version of HIV-1. The kidneys of all primates contain cells called macrophages, in which viruses like HIV can grow. Vaccine-making procedures in the 1950s were rather crude, so if Koprowski did use chimp kidneys, and if these kidneys came from a chimp carrying the precursor of HIV-1, he just might have been growing chimp HIV in his polio vaccine. When African children were fed the vaccine, the chimp virus might have infected some of them through oral cuts or sores or through the mucous membranes in their mouths. When these children grew up, they would have passed the virus to their sexual partners and children, and before long, in Hooper's view, the global AIDS epidemic would be underway.

Versions of this story have been around for a while, although few scientists take it seriously anymore. It was first advanced in 1987 by a disqualified Texas medical doctor called Eva Lee Snead, who later wrote a book called Some Call it "AIDS" - I Call it Murder! The Connection Between Cancer, AIDS, Immunizations and Genocide. A philosopher named Louis Pascal heard Snead discussing AIDS and polio vaccines on the radio and decided to look into it further. He then wrote a detailed research paper arguing that it would have been technically possible for a primate precursor of HIV to have contaminated the Congo polio vaccines. He also criticized the scientific community and the editors of The Lancet and Nature for not publishing his articles [1]. Later the journalist Tom Curtis wrote a more sober article about the polio theory in Rolling Stone magazine [2]. Snead, Pascal, and Curtis argued that if AIDS had crept into the human race while hidden in a polio vaccine, it would not be the first time that something like this had happened. Many polio vaccines from the 1960s were contaminated with a monkey virus called SV40 that is now suspected of promoting various human cancers, including mesothelioma, an aggressive form of lung cancer.

Hooper has taken these arguments considerably further. Hooper is a journalist, not a scientist, but his 850-page book, with another 250 pages of notes, reflects some arduous reporting. He traveled back and forth across Europe and the US, interviewing people ranging from famous AIDS researchers like David Ho and Robert Gallo to the people who worked with Koprowski in the Congo to a group of men sitting outside a bar in St. Louis who might have known someone who might have known someone who probably didn't die of AIDS in the 1960s. The detail is at times fascinating, at times confusing. Nevertheless, The River is among the best surveys to appear on the epidemiology of AIDS.

For Hooper's theory to be true, Koprowski must have been using chimpanzee kidneys to make the African vaccine. Koprowski claims he grew his vaccine in the kidneys of Asian monkeys, not chimpanzees, and that his Congo chimps were used only for testing the vaccine. Everyone else who might have known which kidneys were used to make the vaccine is either dead or can't remember. Some people who were associated with the Congo research in the 1950s remember chimpanzee kidneys being shipped across the Atlantic to a lab across the street from Koprowski's in Philadelphia, although it is not clear that any of them went to Koprowski himself. Koprowski says his papers have been lost and there is no other documentation that might resolve the matter. Hooper found that the earliest cases of HIV and AIDS emerged from the very regions and, in some cases, the very towns and villages in Congo, Rwanda, and Burundi where some of Koprowski's trials took place. Could HIV have escaped from Koprowski's lab and spread throughout the world? [3]

Some scientists feel, like the sailor in Island of Lost Souls, that this is something we might not want to know. David Heymann of the World Health Organization told Curtis that "the origin of the AIDS virus is of no importance to scientists today." Another, rather irate AIDS researcher told him, "Who cares what the origin of the virus is?... It's distracting, it's non-productive, it's confusing to the public...."

Is there any value in knowing where HIV came from? I think there is. HIV viruses crossed into human populations from primates at least twice, and perhaps more often, probably in the 1940s or 1950s or perhaps a few decades earlier [4]. The only way to prevent other chimp or monkey viruses from doing so again is to know how such transfers could occur. And if a group of African scientists came to the US and treated a million people with something that might, however improbably, have unleashed the most hideous plague in living memory, I think we'd want to know.

However, scientists who recognize that it is legitimate to ask how HIV came into being are skeptical of the theory that it came from a polio vaccine. John Moore of the Aaron Diamond AIDS Research Center in New York compared Hooper's polio-AIDS hypothesis to the grassy knoll theory alleging that a second killer from the Mafia, the CIA, or some other agency, and not Lee Harvey Oswald, assassinated JFK [5]. Koprowski himself is adamant that his vaccine could not possibly have started the AIDS epidemic. In October 1992 a committee of AIDS experts investigated the polio vaccine hypothesis and exonerated Koprowski's vaccine. In December 1992 he sued Rolling Stone magazine and Tom Curtis for libel. The case was settled out of court.

The expert committee's decision had put the matter to rest for many observers, including me. But as I was reading The River, I recalled that about ten years ago another committee of experts in the UK concluded that beef from British cows was safe to eat, even though hundreds of thousands of cows were dropping dead from a terrifying and completely new brain disease called bovine spongiform encephalopathy (BSE). Forty-seven British people have already died from a new form of Creutzfeldt-Jakob disease, which they almost certainly got from eating meat from cows with BSE. Many more deaths are likely to follow over the coming decades. A few years before the BSE committee handed down its decision, another committee in France decided to delay the heat-treating of blood products for hemophiliacs and also the testing of blood for transfusions. Hundreds of people who might have escaped infection contracted HIV. So committees are hardly infallible, and sometimes, in order not to alarm or "confuse" the public, they put the public at risk.

2.

Many researchers believe there is a perfectly good explanation for where AIDS came from - that it was what Hooper calls "natural transfer." According to this theory, AIDS is really an old disease, and the HIV viruses were always fairly common in a small number of forest-dwelling communities that hunted monkeys and apes for food. Hunters subduing or butchering their prey would have become infected with the primate versions of HIV if they cut their hands and chimp or monkey blood seeped into the wounds. Because these tribes were isolated in remote villages, however, no one else ever became infected. Then upheavals in African society in the 1950s changed everything. After World War II the far-flung regions of the continent were suddenly drawn together as never before by highways, labor migrations, and refugee movements. It is plausible that these highways for people were also highways for germs.

The African wars of independence, the growth of African cities, new highways and truck routes, and the expansion of African mining industries suddenly drew men out of the countryside. Women, children, and the elderly were left behind in the villages, while their men looked for work, often hundreds of miles away, and prostitution flourished wherever these men went. Now the HIV viruses had many opportunities to escape from the bush, and every urban community, every truck-stop and military barracks, was a breeding ground for HIV. All that was necessary for the virus to break out of the jungle was for a hunter or meat seller to cut his hand while butchering an infected chimp, and then for that hunter to migrate to a city or join an army and have sexual relations, perhaps in a brothel. The virus might then spread from the prostitute who had sex with the hunter to other customers, and then perhaps to other brothels visited by those customers, and then to yet more customers, and eventually to the wives of customers. Most HIV-infected people do not get sick for five or ten years after they are infected. During that time they can unknowingly spread the virus to others.

This is a plausible theory, even though there is something rather Victorian about it. In the nineteenth century, theories about the impact of modern urban life on fragile souls from traditional tribal villages were sometimes invoked to explain why Africans were so susceptible to tuberculosis. Perhaps, for some people, the natural transfer theory suggests that AIDS is the price Africans have paid for independence, war, urban drift, sexual license, and being cruel to chimps and monkeys.

Hooper is skeptical about the natural transfer hypothesis for other reasons, and his arguments are worth considering. Indeed, I found The River most interesting where Hooper examines, and rejects, the "natural transfer" theory, which has been widely accepted since the 1980s. For one thing, Hooper argues, the natural transfer theory does not really explain why AIDS emerged when it did. Africans have been killing and eating monkeys for at least 50,000 years and yet African and colonial doctors, even those who worked in rural health centers, had never seen anything like AIDS before. Moreover, there is no reason to believe that colonial or pre-colonial Africa was all quiet villages and stable families. Certainly prostitution existed in the nineteenth century, as did extensive trade between the interior and the coasts. Since the sixteenth century Africans have engaged increasingly in war, sometimes with European invaders and sometimes among themselves. For example, in the early nineteenth century, land disputes among rival chiefs in Southern Africa ignited the "Wars of Wandering," named for the extensive migrations that followed.

The slave trade, which reached deep into the interior, existed in Africa long before colonial times, and accelerated after the arrival of the Portuguese in the fifteenth century. It has been estimated that between 1700 and 1850 alone, twenty-one million Africans were enslaved, and at least nine million were marched to the coasts and shipped all over the world. During the two World Wars African men were recruited as soldiers to fight in North Africa and the Middle East. These migrations did spread HTLV-1, a virus similar to HIV, that also seems to have come from chimpanzees, as well as malaria and yellow fever. So why not HIV?

Hooper also questions the natural transfer theory because he believes that more than a hunter's wound must have started the AIDS epidemic. HIV-1 is largely absent from the pygmy communities that still live in forests and hunt the very chimpanzees that carry viruses closely related to HIV-1. Pygmy hunters use rough tools to butcher their prey and, if the natural transfer theory is correct, pygmies, if anyone, should be infected with HIV. However, the only HIV-positive pygmies identified so far are those who have had significant contacts with larger towns and probably picked up the virus through sexual intercourse. Pygmies do seem to carry HTLV-l, which also spreads through blood and comes from chimpanzees. If pygmies can contract HTLV-1 from chimps, why don't they contract HIV?

One reason may be that the monkey and chimp versions of HIV may not be harmful to human beings, and may not spread from one person to another. In 1990 a laboratory worker became infected with a monkey virus related to the one that is thought to have given rise to HIV-2 in West Africa. He [6] was working with the blood of a macaque monkey that had been infected with an HIV-like virus from a sooty mangabey. It is not clear exactly how the lab worker became infected, but he had been suffering from a case of poison ivy and the rubber lab gloves hurt his hands, so he didn't wear them. It is likely that he spilled something - blood or some other fluid with virus in it - on his hands and that the virus seeped in through the sores. The lab worker's immune system made antibodies against the virus, but the virus itself seemed to grow very slowly. The lab worker is still healthy, almost ten years after being infected. Similarly, several Africans, including two Liberian rubber plantation workers and a woman who sold monkey meat at a market in Sierra Leone, were infected with the sooty mangabey virus thought to have given rise to HIV-2; but again the infections seem not to have progressed. These people never got sick, and their viruses seemed not to have spread to anyone else [7]. This is virtually unheard of with real HIV infection, which never clears and, as far as is known, always ends in death.

Something probably did happen in Central Africa before the 1960s, and perhaps simultaneously in West Africa, to cause a very small number of monkey viruses that were previously harmless to human beings to become deadly, to change their "chemical rhythm," as Dr. Moreau would say. Somehow they evolved the ability to creep into semen and other secretions, and spread from person to person, and somehow they began to grow so rapidly in human blood that they were able to overwhelm the immune system and destroy it.

What happened, exactly, is still a mystery, and Hooper's polio vaccine theory may not explain it either. First of all, there is no proof, or even a very strong indication, that chimp kidneys were used to make the vaccine administered in Africa. The only person who remembers that chimp kidneys even went to Koprowski's lab is the wife of his technician, who admits that her memory of the period is hazy. She does tell Hooper she is pretty sure some chimp kidneys went to Koprowski's lab, but since no one else remembers this, and since there is no record of what Koprowski did with the kidneys, this is still not much to go on. Moreover, yet another deadly HIV virus may have emerged since the polio vaccine trials ended. The HIV variant known as HIV-1N, which is extremely rare and seems to be found only in Cameroon, may have been transferred from chimps to people only recently.

Hooper's theory also does not account for the crucial step, the mutation of the monkey virus into the aggressive, deadly human virus, HIV. If butchers of monkey meat, pygmies who hunt chimpanzees, and lab technicians who spill monkey blood on their hands seem not to get AIDS, why would people get it from monkey viruses in a polio vaccine?

3.

What did happen? How did an apparently harmless monkey virus turn into a killer? While writing this article I asked several AIDS researchers where they thought HIV came from. Just about all of them said they thought it was an old African disease that emerged from the bush when the winds of change blew through the continent - that HIV was driven by urbanization, war, trucking, mining, and prostitution. While I agreed the virus might be spreading that way, I told them I also agreed with Hooper's view that AIDS just didn't look like an old African disease. It looked like HIV had crossed from primates to people quite recently.

One hypothesis, which Hooper pursues only briefly in The River, intrigued me. A very small number of scientists [8] have quietly been suggesting that HIV may have first started spreading (and may still be spreading) into human populations through unsterilized needles used in doctors' clinics or in vaccination campaigns, or even in blood transfusions. While I was talking to Patricia Fultz, who studies HIV-like viruses in monkeys at the University of Alabama, she mentioned the work of Opendra Narayan, at the University of Kansas. I discovered that Narayan had actually succeeded in turning an apparently harmless monkey virus into an AIDS virus in his own laboratory.

Narayan works with a genetically engineered virus called a SHIV (simian human immunodeficiency virus), which is a version of HIV that is used to infect lab monkeys. This SHIV grows in monkeys but does not cause disease in those monkeys, and it is not passed to other monkeys through sex, biting, or other natural means. However, this SHIV can be passed from one monkey to another artificially in laboratories, for example through blood transfusions or through bone marrow transplantation. If the SHIV is transmitted artificially from one monkey to another rapidly enough, through a process known as "passaging," it can turn into a virus that spreads easily and causes AIDS in monkeys.

"This has been known since Pasteur's time," Narayan told me. "If you take any virus and 'passage' it through a new species often enough, eventually you get a more pathogenic virus." To prove that this would work with SHIV, Narayan and his colleagues [9] injected it into a monkey and waited for it to grow. Usually the monkey's immune system controls the virus and clears it, but this takes a month or so. After a few weeks, Narayan took the virus from the monkey's bone marrow, where it was still growing, and then injected it into another monkey. A few weeks later he took the virus from the second monkey's bone marrow and injected it into a third monkey. The virus caused no disease in the first two monkeys, but it caused mild disease in the third monkey. But when, after a few more weeks, the third monkey's virus was passed to a fourth monkey, the virus caused AIDS in almost every subsequent monkey Narayan injected with it.

Something similar may have happened with HIV. If a hunter or monkey-meat butcher became infected with a harmless monkey virus and then shortly afterward passed it on to someone else, who then passed it on to someone else a few weeks later, it is possible that the monkey virus might have turned into HIV. Like Narayan's SHIV, the monkey virus might not have been able to cross from the hunter to other people by sex, but it just might have been able to cross to others through blood. This might have happened in the clinics and hospitals of twentieth-century Africa.

Perhaps a hunter or butcher carrying a benign monkey virus gave blood at a blood bank or had an injection. Perhaps someone was transfused with his blood, or perhaps the needle used to inject him was used to inject someone else without being sterilized. Perhaps, a few weeks later, the virus was transferred to a third person through another injection or transfusion. This might have been enough to "kick-start" the virus. It might have evolved through such "passaging" to become able to grow vigorously in human cells. It might have been able to infect new people through means other than needles or blood transfusions. It might have become sexually transmitted, and it might have become deadly. Hypodermic needles were introduced in Africa in the early part of this century, and blood banks were introduced later, probably after World War II. I asked Dr. Narayan whether primate HIVs might have first adapted to human beings after being "passaged" through blood transfusions or unsterilized needles, just as his SHIV adapted to monkeys through successive bone marrow transfers. "Yes," he said, "that might have happened."

Such "passaging" events might be very rare. "We used to talk in terms of lightning rods," the AIDS researcher Preston Marx told Hooper. "You know - lightning can't strike twice unless there's a lightning rod. The lightning rod's the needle. That's why it struck twice in the same place - HIV-1 in Central Africa and HIV-2 in West Africa...." Hooper dismisses the hypothesis that hypodermic needles or blood transfusions had anything to do with the origin of HIV, but he does not consider the work of Dr. Narayan and his colleagues.

In our efforts to make things better for ourselves, we sometimes make things worse. If HIV entered human populations through such new medical technologies as needles, blood transfusions, or even polio vaccines, it will not be the first time that a microbe has flourished in the wake of scientific advance. Smallpox, brucellosis, anthrax, and tuberculosis are all cattle diseases, influenza comes from hogs, leprosy from the water buffalo, the common cold from horses, and measles, rabies, and hydatid cysts from dogs. All these diseases probably first affected human beings after these animals were first domesticated and when the density of human populations increased sufficiently to permit these microbes to propagate. Epidemics of polio only emerged in the nineteenth century with improvements in sanitation. Animal husbandry and sanitation have saved generations from malnutrition, dysentery, cholera, and many other plagues, only for new ones to emerge in their places.

4.

Now that the AIDS epidemic is underway, a vital question that remains is why the disease is now overwhelming so many developing countries and remains a serious problem in the US, especially among the poor. In 1998, 5.8 million people contracted HIV, more than two thirds of them in sub-Saharan Africa. Asia is catching up: 7 million Indians now carry HIV, as may as many as 1 million Chinese. In the US, death rates from AIDS are falling as a result of the success of new medications, but the number of new infections seems stable, and may even be rising, especially among women and people of color.

Many governments have been ambivalent about addressing the AIDS epidemic. Countries such as Uganda and Thailand that have invested in comprehensive prevention and information campaigns have saved thousands of lives; still, the virus persists, even in communities that seem well informed. A 1995 survey from Uganda showed that more than two thirds of those interviewed knew how to prevent transmission of HIV, for example through the use of condoms. A simultaneous survey showed that fewer than 5 percent of women had ever used a condom in their lives. Condoms are expensive for people in developing countries, sometimes poorly made, and often hard to find. Men don't like them and it is often impossible for women to insist they be used.

Manuel Carballo, who helped pioneer the World Health Organization's AIDS program in the 1980s, told me he believes HIV "follows the contours of inequality." Early in the epidemic, there was a high incidence of AIDS among relatively prosperous people, including professional people in Africa, and among gay men in the US. But AIDS is becoming increasingly a disease of the poor, both in the developing world and in the West [10]. Poverty, powerlessness, and exclusion are perhaps the greatest risk factors for HIV infection today.

In Uganda a few years ago, I went to see a rehearsal of a rather dark musical comedy put on by a local AIDS organization. The central character and his wife lived in a village near Kampala with their four children. They were poor, but he wanted his wife to have another baby. She refused, and wanted him to use condoms. He went to the city, where he met two girls in a bar. They were even poorer than he was and behind his back they sang about how they looked forward to filling their bellies. One of them became pregnant, and then the man brought both girls back to his house in the village. The girls gave the man HIV, which he transmitted to his wife. In the end, the man, his wife, the two girls, and the girl's baby all died, and the man's relatives all came together in a rousing finale to fight over his property.

The audience consisted of a few locals, friends of the actors, and others who just stopped by to watch. An American woman who worked for the AIDS organization wanted to know what people had thought of the play. "What did you think the message was?" she said, addressing the audience. "Don't go out with bar girls," someone said. "Stick to one partner," said another. Then an older woman spoke up. She worked as a healer and herbalist, and she was wearing a voluminous green basuti, the traditional costume of her tribe. "AIDS has come to haunt a world that thought it was incomplete," she said. "Some wanted children, some wanted money, some wanted property, and all we ended up with is AIDS."

REFERENCES

1. "What Happens When Science Goes Bad: The Corruption of Science and the Origin of AIDS: A Study in Spontaneous Generation," Working Paper no. 9, University of Wollongong Science and Technology Analysis Research Program (Wollongong, New South Wales, 1992).

2. Tom Curtis, "The Origin of AIDS: A Startling New Theory Attempts to Answer the Question: Was It an Act of God or an Act of Man?" Rolling Stone, March 19, 1992, pp. 54-61, 106-108.

3. HIV emerged at least twice in Africa, once around the Congo-Rwanda border as HIV-1, and once in West Africa as HIV-2. The two HIVs differ genetically in that they have similar, but not identical, genes, and those genes are ordered differently in the viral genome. Also HIV-2 is less aggressive than HIV-1 in that it is transmitted less easily, and people with HIV-2 develop AIDS more slowly than people with HIV-1. Koprowski's vaccine, according to Hooper, would only have been responsible for HIV-1. For the origin of HIV-2, Hooper postulates that Dr. Pierre Lepine of the Pasteur Institute conducted polio vaccine trials around Guinea Bissau in the 1950s. Lepine claims to have grown his vaccine in baboon cells, but Hooper thinks he might have used sooty mangabey and that this might have gone unrecorded. On the other hand, Hooper writes, Lepine might have used kidneys from a baboon that had been infected with a sooty mangabey virus.

4. The first confirmed case of HIV infection was in 1959; it is possible that there were a few other cases in the decades before that went unrecorded, but it is unlikely that there were many.

5. J.P. Moore, "Up the River Without a Paddle?" Nature, Vol. 401 (1999), pp. 325-326.

6. Or she: the sex of the lab worker was not reported.

7. Gao et al., "Human Infection by Genetically Diverse SIVsm-related HIV-2 in West Africa," Nature, Vol. 358 (1992), pp. 495-499; Khabbaz et al., "Brief Report: Infection of Laboratory Worker with Simian Immunodeficiency Virus," New England Journal of Medicine, Vol. 330 (1994), pp. 172-177. See also Hooper, Chapter 49, "Preston Marx and the Alternative Hypothesis."

8. See Hooper, Chapter 49, "Preston Marx and the Alternative Hypothesis." Also see Zhu et al., "An African HIV-1 Sequence from 1959 and Implications for the Origin of the Epidemic," Nature, Vol. 391 (1998), pp. 594-597. This article contains the following aside:

The factors that propelled the initial spread of HIV-1 in central Africa remain unknown: the role of large-scale vaccination campaigns, perhaps with multiple uses of non-sterilized needles, should be carefully examined, although social changes such as easier access to transportation, increasing population density and more frequent sexual contacts may have been more important.

9. See S.V. Joag et al., "Chimeric simian/ human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques," Journal of Virology, Vol. 70 (1996), pp. 3189-3197, and also K.A. Reimann et al., "A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in Rhesus monkeys," Journal of Virology, Vol. 70 (1996), pp. 6922-6928.

10. See B. Weniger and S. Berkeley, "The Evolving AIDS Pandemic," in J. Mann and D. Tarantola, editors, AIDS in the World II (Oxford University Press, 1996).