The Origin of AIDS: God or Man?
04-03-2006, 03:25 PM (This post was last modified: 12-01-2009 06:46 PM by achali.)
The Origin of AIDS: God or Man?
The Origin Of AIDS
by Tom Curtis
Rolling Stone, Issue 626, 19 March 1992, pp. 54-59, 61, 106, 108, omitting photos and captions.
A STARTLING NEW THEORY ATTEMPTS TO ANSWER THE QUESTION 'WAS IT AN ACT OF GOD OR AN ACT OF MAN?'
It was almost thirty years ago, but I clearly remember one event on that hot and humid day early in August 1962. Like communicants in some universal mass, my two brothers, my parents and I slowly moved to the head of a very long, snaking line composed of thousands of people - a significant part of the population of Galveston, Texas. All were awaiting admittance into the central hallway of Ball High School so we could approach a simple wooden table - a kind of altar of science - where a volunteer nurse handed each individual a tiny paper cup containing a sugar cube. I gazed intently at mine. One side had a faint yellow tinge and dark specks where the half-cubic-centimeter or so drop of liquid vaccine had landed. Though I was surprised that my cube was so dirty looking, I popped it in my mouth, chewed and swallowed. The rest of my family followed suit. Over the next two years, the same ritual was played out in towns and cities across America. These other patient believers, like me and my family, were seeking not life eternal but science's more secular but no less miraculous promise: everlasting immunity from the most dreaded scourge of the Forties and Fifties - paralytic poliomyelitis. Before the polio vaccines were introduced in the Fifties, the disease had struck about 22,000 people a year in the United States alone - often young children. The new, vibrant medium of television showed kids like us shackled by leg braces and crutches or imprisoned in iron lungs - huge cylinders covering all but their heads. I had an even more terrifying image of the ravages of polio: A close friend of my parents', a vital young physician named Martin Schneider, had contracted the disease in 1948 and would spend the last two decades of his life paralyzed from the waist down and confined to a wheelchair.
In one of the greatest triumphs of twentieth-century medicine, the promise to deliver us from that crippling contagion was kept. The one-two punch of the "polio shots" developed by Dr. Jonas Salk and the oral vaccine developed later by Dr. Albert Sabin effectively eradicated polio in developed countries and later in much of the Third World.
But there was a shadow over the conquest of polio. It's estimated that early on, at least, the polio vaccines administered to many millions of people in the U.S. and around the world were inadvertently contaminated. "We took all the precautions that we knew of at the time," Salk says today. "Sometimes you find out things after the fact."
What Salk and the other pioneers of the polio vaccine found out was that accidents did happen. In the preparation of massive amounts of various polio vaccines - either weakened or killed virus that causes recipients to form protective antibodies - things occasionally went horribly wrong. Hundreds of people actually contracted polio by the very means they sought to protect themselves - and some died. Researchers who cultured the virus using the tissues of animals were stricken and sometimes killed by other viruses infecting the animals. And finally, the medium that scientists used to produce the vaccine - the kidneys of monkeys caught in the wild - was found to be sometimes contaminated by simian viruses that were later passed on to millions of unsuspecting people.
There is the prospect that we may find out something else after the fact: that another polio vaccine may have inadvertently infected its recipients with an even more fearsome and insidious virus, the one that causes acquired immune deficiency syndrome - AIDS.
In August 1991, Blaine Elswood, an articulate AIDS treatment activist and diligent sleuth of medical literature who works at the University of California at San Francisco, mailed me a terse note paper-clipped to several xeroxed items from medical and scientific journals raising the issue. "Here's a bombshell story just waiting for an investigative reporter," he'd said.
We'd had a casual, two-year telephone-and-mail acquaintance ever since Elswood had been recommended to me as a source by a West Coast dermatology professor working on new treatments for AIDS. Clearly a maverick, Elswood was proudest of having confounded "guerrilla clinics," which research and provide alternative drugs for those with AIDS, in San Francisco and elsewhere. Elswood is neither a physician nor a Ph.D., and he has one clear bias: He does not think American doctors will easily acknowledge that medical science itself may have played an unintentional role in introducing AIDS to the human population.
As I soon find out, Elswood is right. When I broach this idea to Salk, who is once again working to develop a vaccine, this time for AIDS, he flatly refuses to discuss the subject. "I don't think I can be helpful to you" he says, "other than to try to dissuade you from pursuing that kind of a hypothesis, because what value is it? What value is it to anyone to try to imply such a cause and effect relationship?" He also makes it clear that he strongly subscribes to another plausible theory: that the AIDS virus has lingered for eons in African jungle tribes and erupted to cause epidemics in recent decades only when those rural peoples migrated to the cities.
AIDS first appeared in equatorial Africa, many scientists now believe. The earliest evidence of its presence on the African continent dates from a plasma sample drawn in 1959 in what was then Leopoldville, the Belgian Congo, and is now Kinshasa, Zaire. Dr. Mirko D. Grmek's definitive book History of AIDS, published in 1990 by Princeton University Press, describes the primary African epidemic's radiating outward from a region located in Zaire and Rwanda. There's also a tantalizing connection with monkeys and other primates: Several African species carry a virus related to the human immunodeficiency virus (HIV), which causes AIDS in human beings. Although HIV has yet to be found in monkeys, a "missing link" simian virus much closer to the human virus has been identified in two wild chimpanzees from Gabon. This has led to speculation that a chimp or a monkey with an AIDS virus identical to the human virus will eventually turn up.
Scientists have proposed a grab bag of ideas to explain how the disease may have leaped the vast chasm from monkey to man. There is, for instance, the kinky-African-sex theory. It involves a bizarre sexual practice in which, to heighten sexual arousal, male and female members of tribes bordering the large lakes of Central Africa introduce monkey blood into their pubic areas, thighs and backs. Then there's the cut-hunter theory, recently described to me by the premier American AIDS researcher, Dr. Robert Gallo. Gallo suggests that since monkeys in Africa are killed for food, a hunter might have nicked himself while skinning an infected monkey and thus might have mixed virus-laden monkey blood with his own; repeated such incidents over time, he argues, could have infected enough people to spark an epidemic. Last Thanksgiving, an Oxford clinician writing in the prestigious British scientific magazine Nature presented another startling hypothesis: that the disease may have sprung from scientific experiments that lasted into the Fifties in which chimpanzee and monkey blood was directly injected into human beings to see if people could carry the form of the malaria parasite that infests those primates.
There are problems with each theory. The first couple are basically speculations that can't easily be con firmed or tested scientifically. Anyhow, those African sexual and hunting practices presumably have been going on for thousands of years; the AIDS epidemic is new. The idea involving the malaria experiments is extremely provocative. It may prove to be more than that if material from the original experiments still exists and can be scientifically checked. But the number of people involved in the tests was tiny: As discussed in Nature, a total of about seventy people received primate blood or primate-tainted human blood during the entire range of the malaria experiments, which ran from 1922 to 1955. Still, AIDS had to start somewhere, so like the other theories, this one has to be considered.
Sprinkled through the medical literature of the last thirty-five years are facts that buttress the unnerving prospect that HIV, the AIDS virus, may have crossed the species barrier as an unintended byproduct of a live-polio-virus vaccine. There was, in fact, an almost forgotten mass-vaccination campaign in which an oral polio vaccine was administered to at least 325,000 people, and perhaps more than half a million people, in equatorial Africa from 1957 to 1960. One of the two vaccines used in that experimental effort was subsequently reported to have been contaminated with an unknown monkey virus.
The timing seems right. A process called genetic sequencing, which tracks the evolution of virus by measuring genetic changes, can read the molecular history of a disease. According to Gerald Myers, the federal government's chief expert in genetic sequencing, HIV dates from about 1960, assuming it arose from a single, common ancestor.
There are natural obstacles preventing a virus from crossing the barrier to become established and thrive in a new species. But it happens. And when it does, the virus frequently becomes much deadlier in the new species than it was in the original hosts.
In recent decades, some scientists believe, live-virus vaccines may have actually helped transfer viruses across species lines. Perhaps the classic example is canine parvovirus, or CPV, which abruptly appeared in dogs in 1977 and within months had become a widespread animal epidemic - or epizootic - on virtually every continent, causing entirely new dog diseases of the intestines and heart muscle. CPV is intriguingly similar in its genetic structure to a cat disease called feline panleukopenia virus (FPLV), but it's even more similar to the vaccine for this disease. This has led several virologists to suggest that by accident or design, the cat virus most likely was introduced into dog cells in the laboratory, where the strain adapted itself to the new host.
A 1989 article in the Journal of the Royal Society of Medicine noted that case and a number of other cross-species transfers of viruses in the context of AIDS. "It would appear," the piece said, "that the AIDS epidemic may be just one of the latest of several mammalian cross-species viral transfers triggered by the techniques of virology developed in the 20th Century, which subsequently spread out of control in the new host species."
To grasp how this possibility relates to polio vaccine used in Africa, it helps to know how polio came to be suppressed in most of the world.
"IT'S NOT GOOD TO KNOW TOO MUCH"
Jonas Salk, backed by a private philanthropy popularly known as the March of Dimes, introduced the first widely used polio vaccine in 1954. His vaccine was a virulent form of the polio virus that had been killed by formaldehyde. This dead, or "inactivated," virus was injected into people to provoke the body's immune system to manufacture disease-fighting antibodies that would repel the wild, paralyzing types of polio. But medical science ultimately rejected Salk's shots as the vaccine of choice in favor of a weakened but still living virus administered by mouth - in Albert Sabin's sugar cube. Unlike the Salk shots, which were believed to require periodic booster vaccinations, the oral polio vaccine conferred lifetime immunity. It could be taken by mouth and required no injections; and the live vaccine silently spread the weakened, non-paralyzing virus even to those who failed to take the oral vaccine. These "susceptibles" would simply catch the weakened virus and get the infection without noticeable symptoms. They also would become immune to paralytic polio.
Polio vaccines are produced by selecting weakened strains of polio virus and then placing them in tissue cultures - live cells from primates. (Either monkey or human cells will work, but researchers selected monkeys because their tissue was more available and there were fears that human cell lines might spread cancer. The unrecognized danger, though, was this: Because monkeys are genetically similar to human beings, some simian viruses can leap the species barrier with devastating effect.) The virus then enters the cell and reproduces itself. All the polio viruses grown to produce the mass vaccines in the Fifties were fed one particularly nourishing medium: fresh monkey kidneys. And throughout the Fifties - a period that was barely beyond the dawn of scientific knowledge regarding tissue culture - some of those monkey kidneys were infected with numerous monkey viruses. Scientists knew about some of these viruses and developed tests to identify and then eliminate the tissues that contained them.
One of the earliest and deadliest was the so-called monkey B virus - a herpes virus first identified and isolated in 1932 by Sabin after it killed a medical colleague at New York's Bellevue Hospital. The unfortunate polio researcher had been bitten by a monkey. "He had developed paralysis after the monkey bite," Sabin recalls almost sixty years later as I interview him in the office of his Washington, D.C., apartment. "He died after a short time." Sabin, who with his full white beard and hair looks a little like Robert E. Lee, continues: "At the autopsy I collected specimens and isolated a virus. Because I was too green behind my ears in virology, I would not accept [it] as being an ordinary herpes virus with which human beings are infected - which a professor at Columbia University, who knew much more than I, did." Chuckling at the memory, he adds, "Sometimes it's not good to know too much."
While working at the Lister Institute, in England, in 1934, Sabin was able to prove that what he had found was a distinct virus. And in 1949, when he was working in Cincinnati, Ohio, he again isolated the virus after another physician researcher was killed by it. "Then, as thousands of monkeys began to be used for the preparation of the Salk vaccine in the early Fifties," Sabin says, ten or so caretakers working with the monkey kidneys or who were bitten while handling the monkeys also developed the same illness and died.
"In monkeys, it's a disease which is as mild as ordinary fever blisters are in human beings," Sabin says, but in humans it paralyzes and kills. "As a result of that, all the [research] monkeys had to be tested." Special precautions were instituted. "But often precautions are not used," Sabin says. Deaths from monkey B virus, though infrequent, have continued, the latest a veterinarian at a south Texas primate facility who died of monkey B virus last fall.
THE FORTIETH MONKEY VIRUS
So monkey B was kept out of the polio vaccines. But there was another monkey virus that polio researchers missed. Between 1954 and 1963, an estimated 10 million to 30 million Americans and scores of millions of people around the world were exposed to a virus that infected the kidneys of Asian rhesus monkeys imported mainly from India. The virus survived the formaldehyde that Salk used to kill his polio viruses. Since 1961 researchers have tested monkeys for SV40 - so called because it was the fortieth such simian virus identified - before using their kidneys for vaccine production.
SV40 was delivered straight into people's bloodstreams along with their Salk shots and via sugar cubes in field trials of the weakened living virus developed by Sabin. Though it was later shown to cause cancer in hamsters and to "immortalize" human cells in test tubes - thus predisposing these cells to cancer - SV40 has not been proven to generate illness in human beings. Nevertheless, researchers at Johns Hopkins recently discovered that when they injected cells treated with SV40 into "nude" mice, which lack an immune system, the mice developed Kaposi's sarcoma-like tumors, similar to those afflicting many AIDS victims. Remarkably, considering the large numbers of people who received the SV40-contaminated polio vaccines, no one has conducted a major epidemiological study in the U.S. to discover whether there is any pattern of illnesses caused by the virus.
Still, there are some troubling statistical associations. In 1968 a scientist in Australia described a correlation between polio immunization and cancers in children past one year of age. Much later, German scientists found evidence of SV40 in 30 out of 110 brain tumors, and later reports indicated a jump in the frequency of brain tumors among those who had received vaccine contaminated with SV40. And SV40 has been associated with other human cancers as well. After news broke about the monkey virus SV40 contaminating some lots of Salk's and Sabin's polio vaccines, congressional hearings were called to examine the explosive issue. On April 14th, 1961, a rival polio researcher of Salk's and Sabin's sent a letter to the House Health and Safety Subcommittee taking issue with growing live polio-virus vaccine in monkey kidneys.
Sounding like someone who had come to his understanding through hard experience, the researcher - Dr Hilary Koprowski of Philadelphia's Wistar Institute - suggested that human cell lines be used instead. "As monkey kidney culture is host to innumerable simian viruses, the number found varying in relation to the amount of work expended to find them, the problem presented to the manufacturer is considerable, if not insuperable," Koprowski wrote the committee. "As our technical methods improve we may find fewer and fewer lots of vaccine which can be called free from simian virus."
But when Koprowski, Salk and Sabin were doing their initial vaccine development in the Fifties, little was known about the simian viruses, and there were no federal regulations stipulating that the viruses be grown in a specific type of tissue culture. No one knew then about retroviruses like HIV that might take years to develop, and so it was assumed that if no viruses had shown up in preparations after a couple of weeks, then those vaccines were clean.
In 1988, when researchers in the Washington, D.C., area reexamined an earlier study run between 1959 and 1965 on nearly 59,000 pregnant women, they found a startling connection: The incidence of brain tumors in children of mothers who'd been injected with the Salk vaccine was thirteen times greater than that of offspring of mothers who hadn't had those polio shots. Stored blood serum from these mothers still existed, and it was retested. The tests seemed to exclude SV40 as the cause. But if not SV40, what about the Salk vaccine might explain the increased risk of brain tumors in offspring of vaccinated women? The researchers asserted that some other infection was probably the culprit. After all, they noted, the Salk vaccine was known to have been contaminated with numerous monkey viruses.
THE MARBURG MONKEY VIRUS
In mid-August 1967, six years after the SV40 problem came to light, a mysterious, dangerous, infectious disease broke out simultaneously in German and Yugoslavian research institutes. Thirty-one people, including technicians making polio vaccines, suddenly became ill - and seven died. All those infected had direct contact with monkeys or their blood, organs or tissue cultures. Other people later got the disease, too, including hospital personnel who had contact with these patients. In one case, a woman contracted the disease from the semen of her husband, who had been infected three months earlier. Though millions of monkeys had been used as experimental animals and as raw material to provide kidneys to make vaccines, no such disease had ever been seen before. Eventually the "Marburg virus" was isolated, and its source was traced to monkeys shipped from Uganda.
But if HIV were one of those numerous anonymous monkey viruses contaminating the early Salk and Sabin vaccines, presumably there would have been an explosion of AIDS in the U.S. outside the currently defined high-risk groups: male homosexuals, intravenous-drug users, hemophiliacs and the sexual partners of those people. Of course, that sort of eruption hasn't happened in the U.S. But it did happen someplace else: in equatorial Africa.
THE CONGO VACCINE
As it happens, equatorial Africa was the site of the world's first mass trials of an oral polio vaccine - a vaccine cultured in monkey kidneys but different in at least one important respect from the Sabin vaccine ultimately adopted worldwide. This footnote in medical history took place from 1957 to 1960 right in the middle of what was then the Belgian Congo, Rwanda and Burundi - the epicenter of the future African AIDS epidemic. It was developed by a naturalized American polio researcher named Hilary Koprowski - the same Dr. Koprowski who four years later would warn congressmen of the dangers of an almost infinite number of monkey viruses contaminating polio vaccines.
Hilary Koprowski, the developer of the vaccines used in the Congo, is a charming deep-voiced man of seventy-five. Born and educated in Poland, where he studied to be a concert pianist while going to medical school, Koprowski began work for Lederle Laboratories in 1946. Like Salk and Sabin he took up the cause of saving the world from polio. He tested weakened strains of the virus in monkeys and chimps and in March 1951 surprised a meeting of polio researchers sponsored by the March of Dimes in Hershey, Pennsylvania. There he revealed that he had become the first physician in history to administer a polio vaccine to humans. The "volunteer" research subjects for Koprowski's live, weakened polio vaccine included twenty children he later described as "mentally deficient" who lived in Letchworth Village, a facility operated by the New York State Department of Mental Health. Later he vaccinated other groups of children, among them the newborn babies of institutionalized women in New Jersey. But a larger test of the vaccine, planned for children of Belfast, Northern Ireland, in 1956, was scrapped amid reports that some of his tamed oral vaccine had reverted to its wild, paralytic form. While no one was paralyzed and Koprowski insists that no one ever would have been, authorities in Belfast feared that such a "reversion to neurovirulence" to use the medical jargon, might spark a new polio epidemic.
After the Belfast debacle, Koprowski who was racing Sabin for the distinction of producing the oral polio vaccine of choice, left Lederle Laboratories to direct Philadelphia's Wistar Institute, then a modest research organization best known for developing a unique laboratory rat. But he held tightly to his goal of producing the winning polio vaccine.
Almost immediately, Koprowski arranged to have his weakened polio viruses tested in a colony of 150 chimpanzees in Camp Lindi at Stanleyville, in the Belgian Congo (now Kisangani, Zaire). To protect the animals' caretakers, these humans, too, were fed the weakened virus. The successful immunization of the keepers then became the justification for mass vaccination trials in the Congo itself- the first mass trials in the history of an oral polio vaccine.
Called by drums, rural Africans traveled to village assembly points. There they lined up and had a liquid vaccine squirted into their mouths. Using this spray method, nearly a quarter million Africans were inoculated in six weeks. Later another 75,000 or so children in Leopoldville, now Kinshasa, got the vaccine, too - though European children living there apparently received their vaccine in capsule form, possibly a significant variation.
From the beginning, Koprowski's campaign was marked by controversy. Trial by Fury, Aaron Klein's 1972 account of the development of the polio vaccines, reports that Koprowski apparently claimed he had the backing of the World Health Organization, but WHO denied sanctioning the mass trial. Koprowski says today that although he was challenged by WHO, he needed only the approval of the Belgian authorities - and there's no doubt he had that. Other preparations of Koprowski's polio vaccines were later used in Poland, Yugoslavia and Switzerland, among other places.
Herald Cox, Koprowski's superior at Lederle, had begun growing the polio virus in developing embryos in chicken eggs. Early on, Koprowski also used the brains of cotton rats to select his weakened strains and nurture the virus. But by 1956 and 1957, when he was readying his vaccine for use in the Congo, Koprowski had long since switched to minced-up monkey kidneys.
Monkey kidneys contained innumerable monkey viruses. Might the one that causes AIDS be one of them? And if it were, would Koprowski's method of delivery - shooting the liquid into people's mouths - be capable of transferring the virus from monkeys to humans?
"You can't hang Koprowski with that," Albert Sabin growls at me. He's sitting at the desk in his study; the walls are covered with testimonial plaques, certificates of commendation and achievement, photos of him with several presidents. Sabin insists that the AIDS virus won't survive swallowing. He's certain of it.
But whether it does or doesn't survive is really not so clear-cut, Dr. Robert Gallo and other retrovirus researchers acknowledged to me; no one knows for sure. Moreover, Gallo's colleague, Dr. William Haseltine of Harvard and also of the Dana-Farber Cancer Institute, in Boston, and others have reported that the AIDS virus infects mucous cells - which of course occur in the mouth as well as in the genitalia .
And Dr. Robert Bohannon of Baylor College of Medicine, in Houston - who in November 1991 reported finding a monkey retrovirus in the tumor of an AIDS patient with no known contact with monkeys - pointed out to me that the process of squirting the polio vaccine in people's mouths would tend to send tiny drops into the air. It might go directly to the lungs or nose and thence to the blood cells it is known to infect.
Later I pose the same question - Could squirting an HIV-laden polio vaccine into people's mouths cause AIDS? - to Dr. Tom Folks, the chief retrovirologist at the Centers for Disease Control, in Atlanta. "Sure it could," he says. "Any time a person has a lesion in his mouth, then there could be transmission if you put enough" of the virus in.
But was there anything to transmit? The answer to that question hinges on the kind of monkeys used to make Koprowski's vaccine.
In 1957, when the Congo trials began, most researchers were using rhesus macaques from India. It would be another four years before scientists fully appreciated the danger that macaques, the natural hosts for SV40, were passing along the virus to humans. Once that troubling discovery was made, in 1961, vaccine producers shifted to kidneys from African green monkeys, which in the wild were free of SV40.
Unfortunately, green monkeys were infected with something else. More than two decades later, in 1982 and 1983, veterinarians at the California Primate Research Center and at Harvard's New England Primate Center observed that large numbers of their macaques were dying periodically of AIDS-like illnesses. These disorders had been killing animals since 1969, but suddenly, the researchers were struck by the similarity to the new disease afflicting American homosexual men. The monkeys' illnesses, the researchers discovered, were triggered by a previously unrecognized retrovirus called simian immunodeficiency virus (SIV).
Among the natural hosts for this virus were none other than African green monkeys, but in that species, typically, SIV didn't cause serious disease. SIV turned out to be related to HIV, though it was only about forty percent similar in genetic structure to the chief AIDS-causing human retrovirus, known as HIV-1. Robert Gallo says some versions of this monkey virus are virtually indistinguishable from some human variants of HIV-2, the second virus that causes AIDS in human beings and mainly afflicts western Africa.
No one who was involved with Koprowski's Congo project and is alive today remembers what kind of monkey kidneys were used in 1957-60. Koprowski is still vigorous and remains at the Wistar Institute, in Philadelphia - now as an institute professor and until 1991 as the director of the facility, which is housed in a stolid Victorian structure on the campus of the University of Pennsylvania.
Koprowski insists that his associates used kidneys from African green monkeys to make the Congo vaccines. When I express surprise and mention that Salk and Sabin were using rhesus monkeys at that point, he agrees to check. When we speak next, he admits he can't find a single paper describing which species was used to make his vaccine. "But I have a suspicion the virus was grown in the rhesus monkey at the original beginning," he tells me in his thick Polish accent. "Now when we switched to green monkeys, I have no idea." Thomas Norton, his associate who grew the virus for the vaccine, is now dead, Koprowski says - as are those who worked with Norton to prepare the vaccine. Significantly, the large lots of the vaccine used in the Congo apparently were prepared at the laboratories of the Wistar Institute, he says. Wyeth Laboratories made subsequent preparations, including those used in Poland.
The question of which monkeys were used to make the Congo vaccine may not be crucial. The virus that causes monkey AIDS occurs in several species, though the original hosts - African greens and others - remain healthy even when infected. Monkeys frequently were gang-caged in those days, facilitating the spread of viruses. If a green monkey turned out to have a virus quite similar to HIV-1, it could have infected the other monkeys.
Although most American researchers in this period apparently did use rhesus macaque monkeys from Asia, for a while around the time Koprowski was working with his vaccine, the monkey supply was interrupted. The Indian government- responding to popular alarm among its people about the widespread slaughter of Indian macaques for vaccine production and other research - barred export of rhesus monkeys to the U.S. For a time at least, that ban must have made suppliers scramble to find different markets and alternate monkey species, probably including African monkeys. Moreover, Koprowski says the kidneys used at Wistar were bought already removed from their hosts, meaning that researchers might not have been sure what kind of monkeys they came from, much less what viruses came with them.
According to no less an authority than Albert Sabin himself, at least one other virus did contaminate Koprowski's vaccine used in the Congo. In 1959, Sabin reported in the British Medical Journal that a special test he had devised revealed the presence of an "unidentified" cell-killing virus in "Koprowski's type 1 'Chat' vaccine used in the Belgian Congo trials." More than three decades later, Sabin says he never figured out exactly what the virus was.
Koprowski insists - as he did at the time in the British Medical Journal - that two other labs examined his vaccine and found nothing except the weakened polio virus. But one eminent polio researcher, Dr. Joseph Melnick, former chairman of the Department of Virology at Baylor College of Medicine, in Houston, who himself developed an oral polio vaccine while working at Yale Medical School, says Sabin probably was right. "Sabin was a very careful worker in the laboratory," says Melnick, a tall, formal, distinguished-looking man. "And I have not known him ever to say that he has found a virus in some preparation that did not exist in that preparation."
In any event, Melnick says, "Monkeys have a very high prevalence of lenti-viruses," one of the subfamilies of retroviruses. "You can isolate it from their tissues, particularly from their kidneys. That is one reason why we stopped using monkeys from the wild and just used home-grown monkeys." Melnick pauses. "It's of interest," he says, "that HIV is a lenti-virus." So are the simian immunodeficiency virus and the so-called foamy virus, both of which widely infect monkeys, Melnick says. "In the early days of the vaccines, we didn't know much about monkey viruses." As for Koprowski's contention that others looked and didn't find the virus in his Congo vaccine that Sabin had noted, Melnick has a simple explanation: "It may not be in one batch and may be in another batch."
A TALE OF TWO MAPS
Writing in the British Medical Journal on July 26th, 1958, Koprowski and his colleagues offered a preliminary report on their mass vaccination campaign. They included in the paper a detailed map showing where nearly a quarter million inoculations had taken place in the northeastern part of the Belgian Congo. The area outlined corresponds roughly to another map in a report published thirty years later in the Reviews of Infectious Diseases - this one identifying the regions of highest HIV infection in equatorial Africa.
Still another paper that appeared in the British Medical Journal in 1985 reviewed HIV infection in the Kivu District, a remote, rural population in eastern Zaire. There, somewhat puzzlingly, the researchers discovered "a high prevalence of antibodies" to the AIDS virus without symptoms of the disease. The Kivu District happens to be where Koprowski's colleagues vaccinated the lion's share of their reported sample - 215,504 children and adults. And there may have been many more vaccinations than initially reported. "Could have been 200,000 more, I really don't know," Koprowski says, because the subsequent mass trials were interrupted by tribal chaos and the civil war that followed independence. No one really knows how those individuals fared over time. No long-term follow-up was possible, Koprowski says.
The researchers who studied the Kivu District in 1985 offered several possible explanations for why the people they found with antibodies for the AIDS virus might not have the disease. The fact that there were more children than adults with antibodies to the virus suggested that the adults could have been exposed in childhood, and some of them might have died or departed from the area. Perhaps, the researchers ventured, if members of a rural population that was biologically adapted to the virus moved into an urban area, exposing a pool of more susceptible adults, this would create "new opportunities for the virus to cause illness in urban adults and the epidemic appearance of the disease in Africa." Moreover, the researchers pointed out that they were looking at a region of "high mortality in childhood, particularly from infectious diseases." Cases of AIDS in children a generation ago simply might have gone unrecognized.
Of course, many of the viruses contaminating the monkey kidneys went unrecognized in the Fifties and early Sixties. Koprowski and his colleagues in the mass-vaccine campaigns found some monkey viruses and eliminated them from their preparations. But many others weren't known, and no test to identify their presence had been developed. "That's the problem," Koprowski says. "The viruses which you know, there's a test - there's no problem; the viruses which lurk, for which there is no test, obviously you can't do anything about."
So, might Koprowski's Congo vaccine have been the vector that unwittingly first unleashed the AIDS virus among people in Africa? I ask the question and Koprowski dismisses the idea with a deep Laugh: "Ho, ho, ho, ho, ho."
I'm asking the question, I say.
He laughs again, this time longer and deeper. "By then you would have had plenty of opportunity to see AIDS in the vaccine," Koprowski says. "You have started in 1960; now it's thirty years. The latency period of AIDS is nine years."
But according to Dr. Gallo, I point out, some retroviruses may take up to forty years to express themselves.
"There is no indication from any part of the world that any other virus occurring there [in the various polio vaccines] causes any problem," Koprowski says.
There are reasons, however, why AIDS in the former Belgian Congo may have been invisible to medical science. In remote, rural eastern Zaire, where most of Koprowski's vaccine was administered, or even in Kinshasa, the disease simply may have passed unnoticed or may not have been identified. "In the tropics, the wealth of lethal infectious pathology is matched by the poverty of diagnostic facilities, rendering undetectable sporadic appearances of AIDS," notes Dr. Mirko D. Grmek, a medical historian, in his recent book History of AIDS. "It is entirely possible that localized or even moderately large epidemics have passed unnoticed."
On the other hand AIDS may have been slow to express itself when it was confined to rural areas where people had fewer sexual partners. A laboratory experiment with monkeys also showed how AIDS may have taken a bit longer to emerge as an epidemic in its present nasty form. When a researcher took a simian AIDS virus from a healthy mangabey, a monkey species in which it typically causes no symptoms, and injected it into a group of macaques, the disease became progressively more virulent each time it passed through the body of another macaque. Finally, this isolated virus even sickened a mangabey, although that species has natural resistance to the original virus. A similar process may have made African AIDS in humans increasingly deadly over time: It's easy to envision a progression in which an original carrier infected by, let's say, a Congo vaccine would have to infect several others before the disease became virulent. Such a process would take time and might explain the lull before the African epidemic appeared (just about the same time the epidemic surfaced in the United States and in western Europe).
THE ZAIRE CONNECTION
In 1987, Belgian researchers writing for a Scandinavian medical journal identified seven AIDS cases originating in Zaire and in nearby Burundi between 1962 and 1976 - well before the African epidemic exploded. Three of these were retrospectively identified as AIDS; the other four were cases in which patients had antibodies for the AIDS virus. Taken together, the authors said, this evidence indicated "that AIDS had already occurred in Central Africa several years prior to its emergence in the United States."
There is yet another curious Zaire connection: its relation to the secondary AIDS hot spot, Haiti. No one knows for sure whether AIDS migrated from Africa to Haiti or from the U.S. to Haiti. But according to Grmek, in the early Sixties, after independence came to the former Belgian Congo, many Haitians worked in Zaire, especially in Kinshasa. The Haitians - who were French speaking, black and had no ties to Belgium - filled the void previously occupied by Belgian colonialists. Their arrival, of course, came only a couple of years after Koprowski's vaccine had been tested in Kinshasa and in remote eastern Zaire.
As for the idea that the Congo vaccine started the African epidemic, Koprowski is skeptical. "Why do you choose Africa?" he asks. "Why don't you compare the enormous number of other countries where exactly the same [vaccine] material was used? Why didn't it start an HIV epidemic there?"
This answer seems to beg the question. Specific lots of a particular vaccine - not all polio vaccines everywhere - might have unintentionally spawned AIDS. For instance, specific batches of Salk's killed-poliovirus vaccine prepared by Cutter Laboratories turned out to be insufficiently inactivated by formaldehyde, and those batches paralyzed 150 of the people who received them and killed 11. Later, specific lots of Salk's and Sabin's vaccines were found to have been contaminated by the monkey virus SV40, with as yet undetermined long-term consequences in people. Why is it unreasonable to ask whether a specific batch of Koprowski's preparation - say, the unique lots prepared at the Wistar Institute solely for use in the Congo mass trials - likewise might have been made from monkey kidneys unknowingly contaminated, in this case by a retrovirus that causes AIDS?
"You're beating a dead horse," Koprowski says. "My opinion is that this is a highly theoretical situation, which . . . does not make sense."
TESTING SEED STOCKS?
Koprowski told me that he maintains the seed stocks - samples of the original vaccines - from the Congo mass trials in freezers at the Wistar Institute. I venture that it would be easy enough to answer the question just by testing those seed stocks.
"Yes," Koprowski begins uncertainly. "But I don't really know how much HIV is really present in monkey kidney.... I have great doubt it would find its way to epithelial cells such as kidney. You are postulating that in the highly processed monkey kidney, you'll get these viruses. I doubt that they are present there."
Later, Koprowski describes for me how the kidneys used in tissue culture were minced up using "scissors or something like that" He is quite correct that HIV and its monkey counterpart, SIV, do not appear to grow in the kidney cells. Instead, as he points out, these viruses are known to grow in lymphocytes and macrophages - cell forms found in the blood. But this doesn't mean that under the right conditions a polio vaccine grown in monkey kidney cultures might not harbor an AIDS virus.
I raise this issue with Tom Folks, chief of the retrovirus laboratory at the Centers for Disease Control, in Atlanta. "You see, the problem with the kidney," says Folks, is that "there's blood and there are lymphocytes that would be contaminating the tissue. So, no matter how hard you try to mince it up - and I've made monkey kidney tissue cultures many a time - you haven't gotten rid of contaminating lymphocytes. So, if the monkey that it's derived from has a pretty fulminant SIV infection, and then they were placing polio [virus] on top of the monkey kidney, but there were contaminated lymphocytes, that is going to be part of the stock. Yeah, it would be there.
"That wouldn't be surprising at all," Folks continues. "And the fact that it's a live vaccine would indicate that they had not gone through any inactivation procedures to denature the AIDS virus, because it would probably denature the polio virus. So, the polio virus is kept alive, and the SIV virus would just travel with it. The theory, the possibility is real. And I don't think anybody would deny it".
The ultimate way to test the idea, Folks agrees, would be to return to the original seed stocks of the vaccine and actually isolate the retrovirus, if any, from the polio vaccine.
Does Folks think there is value in figuring out where AIDS came from? 'I think any time we can learn more about the natural history, it helps us understand the pathogenesis [how the disease process works], and it helps us understand the transmission" Nonetheless, he says: "It's a delicate issue. You're going to put some people on the spot - the person who has the stocks."
Some others in the AIDS establishment - like Dr. David Heymann, who heads the office of research for the World Health Organization's Global Programme on AIDS, and Harvard pathology professor William Haseltine are so hostile to the possibility that a vaccine could have introduced AIDS that they refuse to discuss it. "The origin of the AIDS virus is of no importance to science today," Heymann says in a phone interview from Geneva "Any speculation on how it arose is of no importance."
Haseltine is even more adamant "It's distracting, it's nonproductive, it's confusing to the public, and I think it's grossly misleading in terms of getting to the solution of the problem," he says. "It's over, it's done with, it's very, very, very unlikely it happened that way, and it's another nonsense article. It's the worst kind of reporting, as far as I'm concerned."
But you haven't even heard anything about it, I say.
"I know what that theory is," Haseltine snaps.
You don't think the origin of AIDS is a significant question?
"It's not relevant," Haseltine insists. "Who cares what the origin was? Who really cares? If you want to do something good, write about problems people experience. Who cares where it came from? It's an unanswerable question."
It may or may not be unanswerable, I say.
"I'm not interested in discussing it," he says again, and we end the conversation.
MONKEY VIRUS = HUMAN VIRUS
In AIDS research, and in any inquiry about it, all roads lead to Dr. Robert Gallo, the federal government's preeminent AIDS researcher. Gallo, the embattled chief of the National Cancer Institute's Laboratory of Tumor Cell Biology, in Bethesda Maryland, was more open-minded than Haseltine and Heymann.
Among the reasons Gallo cites supporting what he considers the settled question of the origin of AIDS in Africa was "the greater divergence in people of the virus." "The more divergent a microbe is in a population, the more time it's had to diverge, all things being equal," Gallo says. "The divergence in Zaire is far greater than the divergence in the United States or Europe or anywhere else."
But how did the virus come to infect Africans? Thanks to recent research by Gallo's protégé, Beatrice Hahn of the University of Alabama, Gallo notes, we now know that there are genetic sequences of SIV that are extremely similar to HIV-2, the second identified AIDS virus that afflicts people and is found mostly in western Africa. "In other words," Gallo explains, "the monkey virus is the human virus - there are monkey viruses as close to isolates of HIV-2 as HIV-2 isolates are to each other."
The same is true, Gallo says, of HTLV-1, the human T-cell leukemia virus, a retrovirus he discovered that causes a form of leukemia in people. Genoveffa Franchini in Gallo's lab has found some monkey viruses, specifically simian T-cell leukemia viruses known as STLV-1, which are, Gallo says, as close to most of the human HTLV-1 viruses isolated from the Caribbean islands, southern United States, southern Japan and equatorial Africa as some STLV-ls are to one another.
What does this mean? Logically, it seems to suggest that there may well be a monkey with a virus that exactly matches the one that causes AIDS in humans. So far, however, nobody's found it. The closest counterpart - the so-called missing link - has been found in two chimps from Gabon. But Gallo says that it is nowhere near as close as the two other monkey viruses he described are to HIV-2 and HTLV-1. "Close enough to argue that it might have been a source of entry some decades ago," he says. "But it's not close enough to be called equivalent."
I ask if Gallo thinks a monkey with a virus resembling HIV-1 will ever be found. "I wouldn't be shocked if there was another species where [the virus] was even closer [to HIV than the variant found in the two chimps]," he says. "Nobody would be shocked. It would be interesting and in a sense exciting, but you wouldn't say, I can't believe it."
So I raise the question of whether Koprowski's polio vaccine, if contaminated with a simian AIDS virus, could have passed it on to man.
At first Gallo dismisses the idea. "Chimps have a virus like ours," he says. "The African green monkey doesn't. So, start with the basics, okay? You make an assumption that it's got to leapfrog and change dramatically. Well, that's ridiculous.... SIV from African green monkeys is not real close to HIV-1. So, stop right there. It ends your theory. Period."
But, I ask, if we know some monkeys have a virtual twin of HIV-2, and if some monkeys have a virtual twin of the human T-cell leukemia virus, why wouldn't some group of monkeys somewhere have a twin for HIV-1? Might this monkey virus exist somewhere?
"Your point is well taken," Gallo says. "In support of your contention is the fact that HTLV-1 is a far more ancient virus in man. A very ancient virus in man. You can say that conclusively. There are Melanesians who were never exposed in Europeans until the last fifty years who are widely infected with HTLV-1.... Yet ... yet, there are HTLV-ls that are virtually identical to some monkey STLV-ls, even though it's had much longer to evolve [in man]. Similarly, HIV-2 is probably an older infection in man than HIV-1. Yet there are HIV-2s and SIVs that are almost identical - that are as identical as many HIV-2s are to each other."
"Therefore, you would suppose that in a newer infection of man you would be far more likely to find an identical virus in a species of monkeys," says Gallo. "That's the support of your notion. Very much so. Against it is that a great number of species have been looked at without finding anything."
"Maybe I'll just say I would have expected somebody would have found it by now," Gallo says. "But maybe we just haven't looked at anywhere near enough monkeys. Because I guess you could argue that even a monkey species where we think we know the virus [exists], that it could have a second virus [equivalent to HIV]. And that not all monkeys are infected with that second virus and that we haven't hit the monkey that is."
After pausing for thought, Gallo adds, "I don't think that we can easily come upon that data, though, because there's not a lot of experiments being done on monkeys in the wild in Africa."
A THEORETICAL POSSIBILITY
But even assuming that a monkey version of human immunodeficiency virus exists, Gallo, like Koprowski, initially questions whether it would grow in monkey kidney cells and whether enough virus would be in the preparation to infect people - perhaps through lesions in their mouths, through mucous membranes in the mouths or since the vaccine was sprayed into people's mouths and some of it may have become airborne, through the lungs into the blood system. After hearing how the polio vaccines were prepared and delivered in the Fifties, Gallo concedes that in some fashion this way of transmitting AIDS is "a theoretical possibility." One important issue is whether the virus can be absorbed through mucous membranes. Gallo has his doubts, but Haseltine and others think it can.
Earlier in our talk, before I broached the polio-vaccine theory, Gallo discussed the case of a Norwegian seaman who visited an east African coastal city in the mid-Sixties, became sick with an AIDS-like illness in 1966 and died in 1976 at age thirty after infecting his wife and a daughter, who died shortly thereafter. The family's blood-serum specimens were tested in the mid-Eighties and were positive for HIV.
Gallo reminds me of the Norwegian sailor's case. "That sort of goes against" the theory, he says, noting that the sailor was only known to have been in east Africa, some 700 miles away from Kivu.
The virus "sure traveled," says Gallo sarcastically. He pauses, considering the large numbers of people inoculated with the oral polio vaccine. "It might travel," he says, "but if those are rural people, I wouldn't expect it to travel to east African prostitutes that fast."
"IT COULD HAPPEN"
But the vaccine wasn't administered only in rural areas. It was given to at least 75,000 people in Leopoldville, a port city on the Congo River that was on a major trade route and that was visited at the time by around a million people a year, according to a paper by Koprowski and his colleagues.
After hearing these facts, Gallo pauses and then says: "It could happen."
Well, I ask, based on the circumstantial case alone, wouldn't it be wise to check Koprowski's seed stocks ?
"Sure, why not ?" Gallo says "Certainly it's not a hard thing to do. How can I argue against checking the seed stocks ? I think clearly that would be interesting. You have to say what they [Koprowski and his colleagues] were doing was a good thing, trying to help people."
Absolutely, I agreed. If this happened, it would be as unintended an effect as -
Gallo cuts me off.
"It happens, sometimes, in medicine"
EPILOGUE: AVOIDING FUTURE CATASTROPHES
At my suggestion, Dr. Robert Bohannon of Baylor College of Medicine has already written to Koprowski in Philadelphia requesting samples of his Congo vaccine so that the material can be tested for the presence of extraneous viruses including HIV. Koprowski hasn't yet responded, but the pressure on him to do so may be building. The original source for this story, Blaine Elswood, has submitted a paper to a European medical journal, which has sent Elswood's paper to Koprowski for comment.
Bohannon has also written to the U.S. Food and Drug Administration requesting access to early seed stocks of the Salk and Sabin vaccines. The FDA has agreed to supply seed stocks dating from 1976 on. But Bohannon won't be getting any earlier samples - there isn't enough of this material left. Dr. Gerald Quinnan, acting director of the agency's Center for Biologics Evaluation and Research, tells me that Sabin's original seed stocks from the early Sixties were not tested even by the World Health Organization in the middle Eighties when concern about simian AIDS was high. That was because there are "only a small number of vials" of the preparation, Quinnan says, and tests "might use it all up."
In his 1991 book Virus Hunting, Robert Gallo suggests that probing for the origins of AIDS and especially seeking to find out whether a monkey carries the virus that causes AIDS in people is an important quest. "We may never know for certain the answers to these questions," he writes, "but they are of more than academic interest because answering them may help avoid future zoonotic catastrophes - that is, transmission of disease from lower animals to humans."
Current methods of growing the Sabin poliovirus vaccine "eliminate most of the blood and lymphocytes" known to be susceptible to the AIDS viruses, Quinnan tells me. Preparations are monitored, and that "provides assurance that there is freedom from most agents," he says. As for being sure the stuff is free from all agents, like some new retrovirus we don't yet know about, Quinnan says: "No, you can never prove something absolutely. However, as far as we know, the system we use doesn't result in any extraneous viruses."
Like Salk and Sabin, Koprowski had the best intentions: He wanted to eradicate a debilitating and deadly scourge. But with what we know now, it's clear there was a certain hubris involved in the rough-and-ready campaigns to conquer polio. There is evidence that all three pioneers used vaccines inadvertently contaminated with viruses from a species dangerously close to our own. If the Congo vaccine turns out not to be the way AIDS got started in people, it will be because medicine was lucky, not because it was infallible.
[sidebar] MAN, MONKEYS AND DISEASE
1932: Young Albert B. Sabin identifies and isolates a monkey virus that has killed a polio researcher at Bellevue Hospital, in New York. It is later named monkey B virus.
1946: Hilary Koprowski and his superior at Lederle Laboratories, in Pearl River, New York, begin work on live polio-virus vaccine.
1950: Koprowski tests first polio vaccine on human beings - a live oral vaccine. The virus is grown in chicken eggs and passed through rat brains.
1954: Jonas Salk introduces his killed polio vaccine, made from virus grown in monkey kidneys.
1955: India, reacting to the widespread slaughter of monkeys to make vaccines, restricts exports of rhesus macaques.
1956: Sabin begins testing a live polio vaccine on humans.
1957: Koprowski's vaccine, now grown in as monkey kidneys, becomes the first oral polio vaccine to be tested on a large population - in the Belgian Congo. More than 240,000 are vaccinated in the first six weeks, most in the remote eastern part of the country.
1957: Sabin begins field trials of his vaccine in the Soviet Union. Later, upward of 70 million get it there.
1958: A three-year campaign to vaccinate African children in Leopoldville (now Kinshasa, Zaire) begins. Some 75,000 children receive Koprowski's vaccine.
1959: Nationalist riots erupt in Leopoldville.
1959: The first detection of HIV in Leopoldville, according to two standard blot tests of stored blood conducted in 1986.
1959: Sabin reports that an unidentified monkey virus contaminated Koprowski's Congo vaccine.
1960: Independence and civil war come to the Congo; Belgian workers depart. At least 325,000 Congolese, maybe many more, have been inoculated. No long-term follow-up is done.
1960: First case of HIV, according to a rough estimate based on genetic-sequencing calculations by Gerald Myers of Los Alamos National Laboratory, New Mexico.
1961: Batches of Salk and Sabin vaccine given to millions worldwide are reported to have been contaminated with SV40, a monkey virus that causes cancer in hamsters.
1961: French-speaking Haitians stream into the former Belgian Congo to take over jobs previously held by Belgian colonialists.
1961-62: Sabin vaccine is licensed in the U.S. and becomes vaccine of choice. Koprowski's is frozen out.
1962: Several more AIDS cases originate in Zaire in this year and later, according to subsequent testing. Some scientists believe that AIDS radiates outward in Africa from Zaire.
1967: Marburg monkey virus kills polio researchers in Germany and Yugoslavia.
1980: A new, fatal disease - later identified as AIDS - begins to appear among American homosexual men.
1982: An AIDS-like disease is identified as killing monkeys at California and Massachusetts primate centers; a virus is later isolated as the culprit. The contagions, it turns out, have been wiping out captive monkeys since 1969.
1983: AIDS virus isolated by Luc Montagnier in Paris.
1985: Researchers report finding HIV among remote villagers in the Kivu District, in eastern Zaire.
1987: "Missing link" chimps found with closest thing yet to the human AIDS virus.
1991: Some strains of simian immunodeficiency virus (SIV) are found to be almost identical to HIV-2, the form of AIDS plaguing West Africa. This boosts speculation that a monkey with a virus quite dose to HIV-1 eventually will be found.
1991 (December): Researcher Robert C. Bohannon requests samples of Koprowski's, Salk's and Sabin's seed stocks to check for contaminating monkey viruses. No response to date from Koprowski; limited success with the Food and Drug Administration. - T. C.
06-05-2006, 09:22 PM
The New York Times
June 5, 2006
The State of AIDS, 25 Years After the First, Quiet Mentions
By THE NEW YORK TIMES
On June 5, 1981, in the Morbidity and Mortality Weekly Report from the federal Centers for Disease Control and Prevention, brief note was taken of a peculiar cluster of pneumonia cases in five otherwise healthy gay men.
The item was the first official mention of a scourge that had no name, no known means of transmission, no treatment and no cure.
AIDS, as it would eventually be called, was already spreading fear in America's gay enclaves, where before long half the young men who came of age at the dawn of the gay liberation movement would be infected, stigmatized, ravaged by rare infections and cancers, and die. It soon reached into neighborhoods already burdened by poverty and drug abuse.
For years after that federal report, one of the few certainties was that this disease, to quote other reports, was "invariably fatal." The United Nations estimates that today, H.I.V., the virus that causes AIDS, has infected more than 65 million people, 25 million of whom have died.
Eventually, scientists discovered the virus that caused AIDS and a test to screen for it. They learned the primary routes of transmission — unprotected sexual intercourse, intravenous drug use and prenatal infection. They found a cocktail of medications that slowed the disease's progression, at least in America. In Africa and Asia, AIDS continues to cut a deadly swath.
The difference between then and now is stark for Joan Vileno, a nurse at Montefiore Medical Center in New York. "In those days," she said, "all of our patients died."
Ms. Vileno, 57, said she chose to start her career at an urban academic medical center for the "unique experiences" that setting would provide. But she had no idea how unique those experiences would be. "No textbook could prepare us for what we were about to see," she said.
In the early 1980's, Ms. Vileno held the hands of angry, terrified and scorned patients, mostly intravenous drug users. They were admitted with lethal infections, rarely seen today, that left them gasping for breath, covered with cancerous lesions, blind, demented and wasted to skin and bones.
There were no medications to cure them of a disease then called Gay Related Immune Deficiency, or GRID, although at Montefiore, in the Bronx, the patients were rarely gay. In a study of a drug that proved ineffective, the average survival time of 300 Montefiore participants was eight months.
Today, Ms. Vileno runs a program for AIDS patients 50 and over who have lived long enough to also have the medical problems that come with middle age.
But a quarter-century ago, absent any effective treatment, the staff improvised. "The things we were able to do had nothing to do with our job descriptions," she said.
Many patients were unwilling to come to the AIDS clinic lest they be seen by someone they knew. So Ms. Vileno made house calls. Other patients, shunned by family and friends, all but moved in to the ad hoc clinic — then a bit of borrowed office space with a tiny staff; now a vast and humming operation.
Ms. Vileno once took a toddler home for the weekend so a husband could stay in the hospital with his dying wife. She organized a wedding in the clinic, officiated by a minister married to a staff member.
When funeral parlors refused to handle bodies, for fear of contagion, Ms. Vileno found a willing undertaker and invited him to staff meetings so he would feel like part of the team.
And returning from an AIDS conference in Paris, she went directly to the hospital. Four patients had died that week, one of them estranged from his family. He had designated Ms. Vileno his representative, so the morgue could not release the body for burial without her signature.
"Everything we did was out of the box," she said. "People today think, 'What are you talking about?' But it was a unique point in time, hopefully never to be repeated."
ATLANTA — Lisa Mysnyk describes the man who gave her H.I.V. as "one of those African-American men who can't seem to stay out of jail." Still, she stayed with him for three years. Sometimes they used condoms. Sometimes they did not.
Ms. Mysnyk, who is also black, now knows that "sometimes" can be a very dangerous word.
"I got caught up in the idea that he wouldn't cheat on me," she said.
Just over half of new H.I.V. infections in the United States are in blacks, according to the federal Centers for Disease Control and Prevention in Atlanta.
Three years ago, her boyfriend tested positive for the virus while in prison. The staff made him call all his sexual partners to warn them about their own risk. When he phoned Ms. Mysnyk, he said he had something to tell her, but he could not seem to get it out. She finally heard the news from a prison nurse.
Her boyfriend called two other women that day, both of them younger than Ms. Mysnyk, who was 34.
While she waited for her test results, Ms. Mysnyk, a single mother of two young sons, told the doctor, "If I didn't have the Lord by my side, I'd be a nervous wreck right now."
When the doctor told her she had H.I.V., Ms. Mysnyk started to cry. Her doctor cried with her.
A few days later, she taught her younger son, who was 7 at the time, how to use a condom. She had a no-nonsense conversation with her 14-year-old about sexually transmitted diseases. "I didn't want him to ever have to be afraid," she said.
In the beginning, her own fear centered on how long she would live and what she could do to keep herself alive. "I started taking all these medications," she said, "and I never liked taking pills."
Ms. Mysnyk takes six pills a day, her virus level is undetectable and her immune system continues to be strong. She thinks she could live 30 or 40 more years as long as the drugs keep working.
She imagines that having the virus is a lot like having any other chronic disease. But unlike most other diseases, she knows, H.I.V. can almost always be avoided.
That is why, when she learned that a young woman who lives in her building was coping with a second unplanned pregnancy, Ms. Mysnyk, rather than offering words of sympathy, asked her a blunt personal question: "Do you and your boyfriend use condoms?"
Her neighbor admitted that sometimes they did and sometimes they did not. "Sometimes," Ms. Mysnyk told her, "isn't good enough."
MUMBAI, India — With the strut of a baby-kissing politician, Mrs. Shah strolled down the byways of the red-light district the other day, pausing every few steps to offer a hug and a stern lecture to the prostitutes.
Mrs. Shah — tall and serene at 35, wearing a turquoise sari — began each conversation gently, with a joke or a compliment. A woman's makeup, she might say, was looking nice. Then she would lean in closer, glance around for onlookers, and pull out a pamphlet from the AIDS organization for which she works part time. Pointing at explicit photographs, she fired out her lessons: This is how to wear a condom; this is what an infection looks like.
When her shift ends, Mrs. Shah, who is being identified only by her common last name to help protect her identity, resumes her night job. By midnight, if luck is kind, she will be in a cheap hotel, earning a few dollars from a strange man for what she calls the only work she knows. And because she must survive, Mrs. Shah will fail to tell him — even as she insists on a condom — that she is a prostitute with H.I.V.
The United Nations reported recently that India had become the H.I.V./AIDS capital of the world, its 5.7 million infections surpassing South Africa's 5.5 million. Some Indian officials have disputed that number, but the government has acknowledged that the spread of the virus shows no signs of easing.
AIDS is often cast as an epidemic of bad choices. But it is also, in the life of Mrs. Shah, an epidemic of the choiceless.
Since childhood, she has walked on a path leading, ever more inevitably, to AIDS. At 13, she was forcibly married to a 35-year-old who kicked her out when she complained of his infidelities. Days later, a woman found her on the platform of a Bombay train station and offered to find her a job as a maid. By evening, she had been sold to a brothel for 10,000 rupees, $220 today.
Once, she said, a customer became a lover, married her and took her away. When he needed money, though, she was back on the street. She protested, and he stabbed her in the cheek and back, burned her with kerosene on the belly and legs and shaved her hip-length black hair down to the scalp.
Two years ago, a test found her H.I.V. positive. "I went crazy," she said. She drank and took pills, trying to kill herself. Then social workers approached her, looking for prostitutes to educate about AIDS.
"I had an idea," she said over a cup of tea, "that what happened to me, I would not let happen to other girls."
SAN FRANCISCO — Work on AIDS remains his calling, but the grand emotions of the early years have subsided. Today, both the disease and Dr. Paul A. Volberding, a physician and researcher who is graying and has an arthritic curl to his fingers, have settled in.
Strangers on airplanes no longer accost him with questions about quick cures, and young men no longer die in his arms. Now if a patient dies, he said, "We think we've done something wrong."
Dr. Volberding, 56, who for many years ran the AIDS program at San Francisco General Hospital, now heads medical services at the San Francisco Veterans Affairs Medical Center. These days his AIDS research, like much of the pandemic, is focused on Africa.
"It feels good to do something so clearly needed that improves health so dramatically," he said of his work in Uganda.
Dr. Volberding has been touched by AIDS since July 1, 1981, his first day at San Francisco General, when he treated a 22-year-old gay man with Kaposi's sarcoma, a disease that until then was seen mostly in the elderly. After he came across other cases, Dr. Volberding did what academics often do: He studied them.
Because established physicians lacked the time and often the inclination to take on what was known as the gay disease, the field was wide open. At 31 and with a staff of one (himself), Dr. Volberding opened one of the first clinics anywhere for people with the disease. A year later, with assistance, he began conducting small clinical trials.
"The patients were so much like us," Dr. Volberding said. "We were all young." Many of them, he recalled, listened to the same music. He still keeps an old Grateful Dead poster on his office wall.
In those early years, Dr. Volberding and his colleague, Dr. Marcus Conant, both professors at the University of California at San Francisco School of Medicine, listed every patient in the city on a blackboard. They knew each by name.
Financing was scarce. Dr. Volberding remembered Dr. Conant suggesting that they wait until there were 1,000 cases, and then the government would take notice.
Many researchers thought they, too, were at risk. Both Dr. Volberding and his wife, Dr. Molly Cooke, also a physician, experienced such fears. Once when Dr. Volberding found a blotch on his skin, colleagues had to reassure him it was not Kaposi's sarcoma. All that has changed, too. Today, Dr. Volberding said, he and his patients commiserate mostly about arthritis and aging.
Art is forced by crisis to become political, and so it has been with AIDS, says the playwright Tony Kushner. The early works came in partly as a response to a society that was slow, even resistant, to accept the reality of a new pandemic.
"It was so clearly the dominant culture's mandate that AIDS death and AIDS suffering should be silenced," Mr. Kushner said. "The obvious thing to fight it would be to speak of it and articulate it."
What followed were works like Larry Kramer's 1985 play, "The Normal Heart," and Mr. Kushner's own Pulitzer Prize-winning 1993 drama, "Angels in America."
Only recently, he said, did he begin to reflect on the impact that the early years of AIDS had on the creative culture, especially on writers and artists.
"We were a community that was in a certain sense ideal in terms of responding in an organized fashion," Mr. Kushner said. "As soon as it became an issue of poverty, it lost a degree of organizational support, as soon as it became more or less brought under control in certain ways in the U.S.," he said. "You can't sustain rage for decades."
The great hole in the landscape is hard to comprehend even now, years past the time when AIDS was ravaging the American art world unchecked.
"There's a group of gay men about five years older than me who no longer exist, who would still be alive and producing work, who are gone," said Mr. Kushner, 49. "And there are a number of people I know who survived the epidemic but who in a certain sense didn't survive, who entered a permanent state of mourning."
Twenty-five years ago, Lawrence D. Mass was running an addiction treatment program in Manhattan for Greenwich House, a social services group whose clients included drug abusers and gay men.
Fertile ground, it turned out, for first documenting the disease that would become known as AIDS.
A little-known physician, Dr. Mass wrote what AIDS chroniclers regard as the first article on the emergence of — well, of something unusual and terrible, but exactly what was not clear at the time. The article appeared in The New York Native, a small weekly written for a gay audience, on May 18, 1981, several weeks before the first scholarly journal weighed in.
Dr. Mass, who is gay, went on to become a founder of Gay Men's Health Crisis and to devote much of his life to fighting the disease he had stumbled onto.
In early 1981, Dr. Mass, then 34, had heard fragments of rumors about strange health problems cropping up in Lower Manhattan, especially among gay men. He found Dr. Steve Phillips, an epidemiologist with the Centers for Disease Control and Prevention, who was following the new mystery. Based on his conversation with Dr. Phillips, Dr. Mass wrote a short article about "rumors that an exotic new disease had hit the gay community."
There was so little anyone knew at first, and so much that people got wrong. But looking back, said Dr. Mass, who still practices medicine in Manhattan, there is one essential truth he believes he had right all along.
"From the start, I said you need to acknowledge our civil rights, you need to recognize our relationships, to have any chance of containing and preventing AIDS," he said. "Shame and fear make it worse."
PROVINCETOWN, Mass. — Jay Critchley's recollection of what happened when AIDS first hit this gay-friendly town on the tip of Cape Cod is clear and stark.
"People just disappeared and died," he said. "It was that dramatic, and it was frightening."
It was common to see men with lesions walking in and out of the shops, bookstores and restaurants that line the town's main street, struggling to breathe the salt air, said Mr. Critchley, an artist and massage therapist. Asking someone if he had lost weight was taboo; it meant asking if he was sick. Friends made sure to stay in close contact, because those who fell out of touch were usually dying.
The town's gay residents drew together and cared for the sick. Many went house to house, making sure they were comfortable, safe, well fed. Still, no one understood the provenance of the suffering, and when investigators from the federal Centers for Disease Control and Prevention came to town on a fact-finding mission, many gay men simply assumed that they, too, would get sick and die quickly.
"There was a time when I just waited for it to happen to me," said Tom Sterns, an antique shop owner and 30-year resident. "There wasn't any point in getting tested because they couldn't do anything for you, and I didn't want to face having it."
In the mid-1980's, he finally got tested. The results were negative.
AIDS changed Provincetown itself, for good and bad. In the summer of 1983, many tourists stayed away, fearful of contracting the disease. But gay men in the once carefree community grew cautious about unsafe sex, Mr. Critchley said.
As advances in drug treatment have allowed infected men to lead longer, productive lives, the disease is no longer visible, Mr. Sterns said, and is not in the forefront of every gay man's mind.
But that is leading to more problems, said Mr. Critchley, who sees more men slipping back into careless sexual practices.
With the reduction in fear, the town too has changed. Rising real estate prices and an influx of tourists have chipped away its neighborliness and bohemian flair.
"The town is so dramatically different now than it was 10 years ago," Mr. Critchley said.
12-01-2009, 02:49 PM
Where did Aids really come from?
Where did Aids really come from?
A 10-year investigation suggests that HIV can be traced to polio vaccine. But the theory is fatally weakened by new evidence, says Roger Highfield
A ROYAL Society meeting to discuss one of the biggest medical mysteries of all - the origins of Aids - climaxed last week in the most remarkable media brouhaha in the scientific academy since it was founded in 1660.
Under the lights of television cameras, before a forest of microphones, and witnessed by a sweltering press pack, one scientist denied he was a mass murderer; a journalist rejected the claim that his theory might put lives at risk; and hacks groaned when one of their number revived the laughable idea that Aids was born when germ warfare research went horribly wrong.
Last year, the mystery was supposedly solved by Edward Hooper, a former BBC journalist. In his vast tome, The River, he built a mountain of evidence that suggested Aids could be traced to the time when Prof Hilary Koprowski, and Dr Stanley Plotkin, developed an oral polio vaccine called CHAT.
Hooper said batches of the vaccine may have been grown in chimp kidney cells in the Congo, the Wistar Institute, Philadelphia, and Belgium. That way, he contended, the vaccine was contaminated with chimp SIV, the ape version of HIV-1 (the most common Aids virus). The vaccine was administered to about a million people in what was then the Belgian Congo, Rwanda and Burundi between 1957 and 1960: thus, Aids was born.
Hooper cited various evidence: an apparently strong geographical association between early cases of Aids and where the vaccine was used; the fact that Prof Koprowski never stipulated which primates he used to grow his vaccine and that chimp kidney was an obvious choice; and that relevant records and vaccine samples have disappeared from labs and government archives.
The case made by his 10-year quest, which left him £40,000 in debt, was circumstantial. But it was enough to enlist a powerful ally in Prof Bill Hamilton, who helped to organise the Royal Society meeting. Unfortunately, while seeking direct evidence in the jungle, Hamilton succumbed to malaria and died earlier this year.
Last week, Hooper produced new evidence. He cited Louis Bugyaki, a vet from Stanleyville in the former Belgian Congo, now Kisangani, who said he had been told that chimp kidneys were harvested to be sent to America, possibly to make vaccine. Hooper declared "two smoking guns have emerged in the last two months". The vaccine developers had erected "a smokescreen" and had refuted only "minor details".
Sceptics remarked that, though intriguing, Hooper relied too much on hearsay and too little on hard fact: extraordinary claims need extraordinary evidence. "There is no gun, there is no bullet, there is no shooter, there is no motive," said Dr Plotkin. "There is only smoke created by Mr Hooper."
Dr Plotkin has prepared a counter-attack. Hooper claimed the first Aids cases coincided with CHAT vaccination campaigns. But Dr Plotkin says that the first cases clustered in towns, which is hardly surprising for a sexually transmitted disease: "The opportunity for sexual transmission and prostitution is higher."
Unusual cases that were highlighted by Hooper as being linked to the vaccine are disputed by Dr Plotkin. In one, he claims the vaccine was used on children, when Aids was recorded in an adult. Another was attributed to a vaccination trial actually done 500 miles away and Dr Plotkin says Hooper "misinterpreted the location of the town".
Hooper even suggested that the Aids epidemic was seeded in America when infants of New Jersey prisoners were vaccinated with CHAT. But Dr Plotkin says he approached the doctor who diagnosed the first Aids cases and found they were not the same as the vaccinated infants.
Dr Plotkin also pointed out that one lot of the CHAT vaccine tested in the Congo (lot 13) was also used in the United States and Poland: yet no Aids cases resulted. Plotkin's attack shifted to Hooper's claim that chimpanzees were used. A colony was indeed kept by Prof Koprowski for vaccine tests near Stanleyville. The reaction of the apes to CHAT was safety tested before trials on people.
The provincial laboratory there was "primitive" and incapable of making vaccine, said Dr Plotkin. Nor do records suggest it was used to cultivate chimpanzee cells. The head of the virology lab and two other witnesses told Dr Plotkin that they had never thought of doing it. He found 40-year-old papers that refer to the use of "monkey kidney" - not ape (chimpanzee) kidneys - when macaque cells, which do not carry SIV, were freely available. "Why would you use chimpanzee cells?" said Dr Plotkin.
He tried to find out, approaching 16 members of the team that made CHAT. All denied that chimpanzees were used, only macaques. Some seemed to retract what they had told Hooper. At the meeting, Abel Prinzie and Paul Osterrieth of the Stanleyville Lab, were vehement that they had been misrepresented in The River.
During the press conference, Hooper claimed some witnesses had been approached with pre-written statements, which they refused to sign. One doctor who had signed had been dying from both Alzheimer's and Parkinson's disease: he was too ill to know what he was endorsing. Dr Plotkin responded that the witness was recovering from a respiratory infection, was lucid, and had been fit enough to return home before he died. He invited Hooper to inspect the transcripts used to draw up the statements.
Psychologists have known for years that eyewitness evidence is fallible. Conspiracy theorists would also argue that the vaccine developers would, of course, deny all charges. Scientists, on the other hand, are not content to rely on anecdote. They want hard evidence. Earlier tests on CHAT had found no HIV or SIV. But Dr Plotkin, among others, insisted on new tests in the wake of The River. Seven 40-year-old samples of the vaccine, including lot 13, and controls were prepared and blinded. Independent labs in France, Germany and the States did the tests. One looked for Aids-related virus, a second assessed the animal tissue used to make the vaccine. A third did both tests.
Prof Claudio Basilico of New York University unveiled the results. There were no traces of SIV, HIV-1 or evidence that the vaccine was made from chimpanzee cells. There was nothing to back the vaccine hypothesis, he said. But he doubted this would satisfy Hooper: "It is somewhat difficult to disprove a theory which is not based on any fact." Hooper countered that different batches were made in different labs and the tested batches did not include one used in the Congo.
The River came in for another attack from Dr Bette Korber of Los Alamos National Laboratory, New Mexico, and Prof Beatrice Hahn of the University of Alabama. "We don't rely on people telling us anything. We rely on the genetic sequence, which is like a fossil," said Prof Hahn.
To date, the only SIV closely related to HIV-1 has been isolated from chimpanzees from west central Africa, coinciding with the epicentre of the HIV-1 pandemic, while the Stanleyville chimps were captured in central equatorial Africa.
Studies of HIV at the molecular level "provide the clearest evidence about the origins of Aids", the meeting was told by Prof Paul Sharp of Nottingham University.
Hooper has tried to explain away the link between HIV and west central African chimps by saying that their SIV led to one group of HIV-1 (denoted N) but the more common, M group, of HIV was triggered by CHAT. This is "fallacious", claimed Prof Sharp, arguing that both M and N groups are equidistantly related to West Central African chimp virus: they were born in the same place. Hooper "does not understand how to interpret the evolutionary trees".
Differences in HIV and SIV, and knowledge of the virus mutation rate, can be used like a molecular clock to work out when the common ancestor emerged. This suggests that the "Eve virus" was probably born long before CHAT. Dr Korber explained that, given the diversity of Aids viruses today (there are 12 subtypes, plus minor variants), Eve emerged before 1940. Verification came from Dr Anne-Mieke Vandamme of the University of Leuven, Belgium, who used different methods and data. Hooper argued that different chimp SIVs may have crossed to humans in 1957-60, through different CHAT trials. In other words, he believes that many subtypes emerged to infect the Stanleyville chimps so the common viral ancestor - Eve - was in a chimp, not a human.
This version of the genesis of Aids would mean dozens of divergent viruses would have had to contaminate the polio vaccine, said Prof Sharp. This seems a profligate use of animals, given that a single kidney can be used to make 100,000 doses of vaccine. Also, if many strains had been used, and if there had been such a high rate of infection, there would have been a high rate of recombination - splicing - of virus types. But the evolutionary tree of group M shows distinct virus subtypes and little recombination during their early diversification. Prof Sharp also described new studies of how SIV turned into HIV which suggest that the protein coating of the ape virus adapted to humans "long before" Hooper claims that people were infected.
Yet another problem for Hooper was described by Dr John Beale: vaccine preparation would most likely kill SIV and HIV (the kidney is broken up using trypsin, an enzyme that would damage the viruses, as would the heat treatment and cycles of freezing and thawing).
The closing speech - described by one delegate as a "devastating critique" - was given by Prof Robin Weiss of University College London, co-chairman. Afterwards, Prof Weiss said that, if it had come to a vote, Hooper would have lost overwhelmingly. Hooper counters that the meeting was set up. "More than two dozen of those present have since contacted me to express disquiet at the way that certain sessions were loaded, at the last minute, with opponents, and to comment on Prof Weiss's partisan closing speech."
A "concerted effort" was made to annihilate his theory "and that effort failed", he said. The sceptics would convince him only if they found HIV samples that predate the use of CHAT (the oldest infection has been traced to the Congo in 1959).
Given that, even today, refrigeration is hardly commonplace in Africa, this apparently reasonable request for hard evidence is a tall order. Prof Weiss was "partisan" because, despite Hooper's protestations, many scientists now believe that his case is contrived and has been fatally weakened by the new evidence.
The great irony is that polio was considered an Aids-like crisis of the time, said Prof Koprowski, who tested CHAT on himself and his children. He complained that he had been dubbed the "father of Aids", and that Hooper's "fantasy" is even today harming efforts to combat polio in Kenya, where mothers have been warned by the church that polio vaccine is contaminated with HIV. Half a century after he fed the first vaccine to a child, one of the greatest efforts to eradicate a disease "may now be compromised".
So what did cause Aids? The prevailing theory is that a hunter or bushmeat seller became infected after being exposed to chimp blood when capturing or butchering the animal. This remains the easiest way to explain the molecular data: a single transfer of SIV to a human in around 1930. But it is not the only possibility. Prof Charles Gilks told the meeting that chimp blood was used to give patients chimp malaria, to induce a high fever to "cook" bacteria that cause syphilis. Aids may have been spread by the widespread reuse of unsterilised needles in the fight against syphilis during the Fifties, added Preston Marx of Tulane University, Louisiana. It was between the world wars that the price of syringes dropped to the point that they were used widely, but remained expensive enough to encourage reuse.
This could explain more than the spread of HIV-1: it may account for the emergence of HIV-2, the less common Aids strain, which is most closely related to a virus that infects another monkey, the sooty mangabey, in west Africa. But these ideas are speculative. The origins of Aids remain mysterious
12-01-2009, 03:08 PM (This post was last modified: 12-01-2009 03:09 PM by achali.)
How it began: HIV before the age of AIDS
How it began: HIV before the age of AIDS
As soon as HIV was identified in 1983, scientists started trying to understand where it had come from, when it had arisen, and why it had spread. Were they too late? To answer most of their questions, they would have had to witness the virus's evolution. Scientists can track new pathogens such as SARS and avian flu because they produce obvious symptoms almost immediately. But HIV is a stealth virus that takes as many as 10 years to present symptoms; by the time researchers knew enough to wonder about its origins, those origins were in the distant past.
For the last 23 years, scientists have been trying to peer into that past. Jon Cohen, a correspondent for Science who has written extensively about the virus, compares the work to fossil hunting, using a few precious shreds of evidence to construct a possible history. "Everybody's always looking for certainty. It doesn't exist [in this field]," he says. "In a sense it's all theory."
Nonetheless, the theory rests on facts, and at least a few of them are undisputed -- including, most significantly, HIV's family tree. There are two species of the virus, HIV-1 and HIV-2. The first evolved from a simian immunodeficiency virus (SIV) found in chimpanzees, while the second came from an SIV in a type of monkey called the sooty mangabey.
HIV-1, which is responsible for the vast majority of AIDS cases worldwide, is divided into three groups -- the "major" group M, and the much rarer "outlier" group O and "new" group N -- that have diverged over years of mutation and evolution. Within the M group -- which makes up 90 percent of all infections worldwide -- there are at least nine strains, known as "clades," of HIV-1 that are constantly mutating and merging with each other, creating yet more new varieties. "The M group epidemiologically has overwhelmed what else is out there," says Dr. Beatrice Hahn of the University of Alabama-Birmingham, who has conducted much of the research into HIV's origin. HIV-2, on the other hand, is not as virulent and largely confined to West Africa, where it originated.
In May 2006, an international group of researchers led by Hahn answered two major questions about the origin of HIV-1 M, the deadliest and most widespread form of the virus: Where was its cradle, and what kind of chimp did it come from? Answering the questions was literally messy work -- researchers collected 599 waste samples from wild chimpanzees and analyzed the viral particles they contained -- but the results were immaculate. Three populations of Pan troglodytes troglodytes living in southern Cameroon provided the crucial data. Two of those populations currently carry SIVs that are molecular dead ringers for HIV-1 M, while many chimps in the third group are infected with an SIV remarkably similar to HIV-1 N. Group O's simian sibling is probably lurking in other chimp populations in West Central Africa, says Hahn, adding that she has "a pretty good idea where it's going to be … and we're going to find it."
The research puts to rest decades of speculation about the birthplace of most types of HIV and their animal "reservoir" in the wild. But there are still many questions that haven't yet been definitively settled -- questions such as:
When did HIV-1 first start spreading in humans?
HIV-1 is surprisingly old, and it probably "debuted" in humans at least three separate times -- one for each subtype, M, N, and O. Scientists' best guess is that the precursor of the most common "M" virus jumped from the Cameroon chimps to humans sometime before 1931. Using samples of HIV-infected tissue harvested over the last three decades, virologist Dr. Bette Korber of Los Alamos National Laboratory has calculated that an ancestral form of HIV started spreading, slowly at first, in humans about 75 years ago. The actual jump from chimps to humans probably occurred shortly before that, says Hahn: "There's no reason to believe this was just lingering around in people."
Korber's model estimates a virus' age based on how extensively different strains have mutated. HIV is an unusual virus; it changes its DNA by both mutation and, more often, recombination, when two strains merge within the body and exchange genetic material. Some scientists refer to this process as "viral sex," and it may partially explain why it is so hard for scientists to make a treatment or vaccine. Korber's model does not take recombination into account, but given a virus' DNA configuration, it can roughly predict the age of that strain. Korber has tested the oldest known HIV sample, taken in 1959, and derived the 1931 estimate.
Why do scientists look at recent samples of HIV to determine the virus' overall age? Wouldn't it be better to use older samples that haven't had as much time to mutate?
It would, but scientists don't have that luxury. Other than the 1959 sample, there are very few preserved specimens of HIV-infected tissue that predate the early '80s, when the virus was first recognized by health authorities. Researchers still hope there are forgotten samples in African freezers. "There has to be some serum or plasma somewhere, and given modern technology we could fish out the virus," says Dr. David Ho, director of the Aaron Diamond AIDS Research Center and one of the world's leading authorities on HIV.
But even if those samples are found someday, they won't necessarily yield definite answers about the virus' age, says Korber: "Often, you can't get anything out of samples like that." Most African samples are made of blood serum, and serum samples contain viral RNA, which degrades much faster than the DNA found in tissue samples. In fact, says Ho, the 1959 sample, which was sequenced by his laboratory, was kept in a freezer but still didn't survive the ravages of time. "It was completely dried up," he says. "We were only able to get small pieces [of genetic material], and we had to stitch them together."
So scientists have estimated when and where the most deadly type of HIV started infecting humans -- but how did it do that?
Most AIDS researchers believe that the "bushmeat trade" allowed the HIV-1 virus, and separately HIV-2, to enter the human bloodstream several times. Hunters who kill and butcher chimps and monkeys are regularly exposed to animal blood teeming with SIVs. If the hunters have cuts, bites, or scratches -- and given the nature of their work they almost always do -- they can catch the viruses from their prey. Hunters going after chimps in Cameroon could have caught the first strains of HIV-1. Sooty mangabeys, hunted and kept as pets in West Africa, could have transmitted HIV-2 to humans.
Africans have hunted chimps and monkeys and kept them as pets for centuries; they've presumably been exposed to SIVs during most of that time. But the conditions needed for HIV to spread widely weren't in place until after the continent was colonized and urbanized. The first victims would have found it easier to unwittingly spread the virus to sexual partners far and wide as roads and vehicles started connecting previously isolated villages and cities. Hospitals may have played a role, too. Strapped for cash, some of them probably re-used dirty needles, unknowingly infecting patients in the process.
Are there other theories about how the virus could have gotten into humans?
There are several competing theories, ranging from implausible conspiracies to arguments grounded in extensive research. The best-known of the latter, the "OPV/AIDS" theory, was exhaustively detailed in the 1999 book The River, by author Edward Hooper. As many as a million Africans were given oral polio vaccines (OPV) between 1957 and 1960. Hooper says witnesses have told him that a few batches of those vaccines were "grown" in chimp cells at a lab in Kisangani, a city in the Democratic Republic of the Congo -- and that the chimp cells, and thus the vaccines, could have contained SIVs that jumped into humans. "There are highly significant correlations between the places where this vaccine was administered and the places where … AIDS first appeared on the planet four to 20 years later," Hooper says.
The majority of HIV researchers subscribe to the bushmeat theory and raise several arguments against the OPV theory. Hahn's recent research confirming that HIV-1 M and N arose from Pan troglodytes troglodytes chimps in Cameroon presents one problem: The Kisangani lab is in the Democratic Republic of the Congo, and it's home to a different subspecies of chimp than the one that was the source of HIV-1 M and N. However, it is possible that the chimps used in the Kisangani experiments were not from the area. In the spring of 2006, Hooper found a paper indicating that at least one of eight chimps at the Kisangani lab was a Pan troglodytes troglodytes.
The 1959 sample also presents a problem for the OPV theory. Judging by how fast the virus mutates, it had already diverged significantly from its SIV ancestors by the time doctors extracted it from a patient. However, the African polio vaccination program had begun only two years earlier, so under the OPV theory, the virus would have had only those two years in which to evolve. Dr. Ho, who sequenced the sample, says it looks like the virus has been around a lot longer than that.
Proponents of each theory have acknowledged (albeit grudgingly) that the other is scientifically possible. In the last two years researchers have found that both "simian foamy viruses" and at least two types of retroviruses can and do jump from monkeys to humans via hunting and butchery. And no one doubts that a vaccine cultured in primate cells could be contaminated with a primate virus. Some early polio vaccines contained SV40, a simian virus discovered in 1960, and the RNA virus that causes Marburg hemorrhagic fever.
The question is not whether either scenario could have happened -- it's which one did. To truly disprove the OPV theory, Hahn says, researchers would have to find HIV-infected human tissue samples that predate the polio vaccine trials. To prove the OPV/AIDS theory, on the other hand, they'd have to find the ancestral SIV in batches of the vaccine that were made in Kisangani. Neither of those things has happened, and it's possible they never will.
Why do we care? Does all this research into how the virus got started tell us anything about how to stop it?
Research into the HIV's origins may eventually yield practical results. It could help scientists understand why HIV's viral ancestor, SIV, doesn't kill or even sicken chimps who carry it. With that knowledge, researchers might be able to make drugs with fewer side effects, or broad-spectrum vaccines that protect against all the strains of the disease that infect people today.
Korber suggests that in an era of emerging diseases, looking back on the virus' shadowy origins offers a "history lesson," or perhaps even a fable, with a moral attached. By the time doctors realized that HIV/AIDS existed, it had already taken up permanent residence in humans. They couldn't have known about it before then, but, Korber says, at least now they know to be wary as the virus continues its shape-shifting spread around the globe. "The fact that it could be with us for quite a long time before we even realized it was there is kind of eye-opening," she says. "I think it's something to keep us on our toes. It helps us understand that we can be surprised." And of course, HIV research may have a few surprises left for us, too.
01-12-2010, 12:54 AM
RE: The Origin of AIDS: God or Man?
Hi to All,
Thanks for sharing this information with us.
I have gained knowledge from this that I do not know.
Keep sharing useful information with us.
02-20-2010, 08:24 AM
RE: The Origin of AIDS: God or Man?
Great article to read out regarding the origin of Aids even i also blame is the Man is the origin of these disease.
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