COLUMN ONE : A Deadly Virus Hides Its Past : The latest theories on the origin of HIV, while drawing skepticism, renew interest in the beginnings of the AIDS epidemic. Primate-to-human transmission is the best guess, but exactly how?
One of the compelling mysteries in the quest to understand AIDS is the origin of the human immunodeficiency virus, which causes the deadly disease. There has been no shortage of provocative theories, ranging from the intentional spread of the virus by a variety of intelligence agencies to one about sexual practices involving the injection of monkey blood.
The latest debate erupted last month. A free-lance journalist, writing in Rolling Stone magazine, advanced the theory that AIDS was transmitted to humans in the late 1950s through a batch of experimental polio vaccine prepared in monkey kidneys and sprayed into the mouths of hundreds of thousands of people in what was then the Belgian Congo.
And a New Hampshire attorney, writing in The Lancet, a British medical journal, suggested that contaminated polio vaccine may have transmitted HIV to some gay men in the United States in the early 1970s. The attorney said that some gay men were prescribed multiple doses of the oral vaccine every month for the treatment of recurrent herpes infections.
AIDS researchers have quickly gathered evidence that casts doubt on these theories. But the publicity has renewed interest in the beginnings of the AIDS epidemic, which some say is a key piece of the puzzle in the search for effective treatment and a vaccine.
Most leading researchers in the field believe that human immunodeficiency viruses arose from a variety of non-human AIDS-like viruses, most likely those found in African monkeys or apes. The cross-species transmission may have happened as recently as 40 or 50 years ago, or decades earlier. It may also still be occurring.
Scientists hope that further investigation of primate-to-human transmission will lead them to the long-sought “ancestor viruses” of AIDS.
“The overwhelming amount of data would point to cross-species transmission (of AIDS viruses) from African monkeys to man,” said Dr. Philip Johnson of Ohio State University in Columbus, a leading researcher in the area. In parts of Africa, monkeys are kept as pets, hunted for food and trapped for export.
The evidence is strongest for a variant AIDS virus, known as HIV-2, which is common in West Africa. HIV-2 can cause AIDS and other life-threatening illnesses, but it is believed to be less virulent than HIV-1, the dominant AIDS virus throughout the world.
So far, the links to non-human primates are weaker for HIV-1. This is because researchers have yet to identify its likely animal ancestor.
Nevertheless, many scientists are convinced that it is only a matter of time until such an ancestor virus is found. The genetic material of HIV-1 differs by as much as 50% from the genetic material of AIDS-like viruses found in monkeys.
By comparison, HIV-2 is closely related (about 20% different), and in some instances nearly identical, to a virus carried by the sooty mangabey, a West African monkey. The sooty mangabey inhabits the same coastal regions of West Africa where HIV-2 is found. About 10% of mangabeys caught in the wild are infected with AIDS-like viruses.
“It is virtually certain that HIV-2 came into humans from monkeys,” said Max Essex, chairman of the Harvard AIDS Institute.
In some areas of Africa, Essex said, “people eat monkeys. When they eat them, they catch them alive because they don’t have refrigerators. They keep them around the settlements. . . . The person butchering the monkey has a sharp knife, is covered with monkey blood and would have ample opportunity to have monkey blood cells contaminate a cut wound.”
According to Dr. Beatrice Hahn of the University of Alabama in Birmingham, “the hypothesis is that HIV-2 infection is a zoonosis, a disease transmitted under natural conditions from animals to man.” Because contact between the sooty mangabey and humans is common, researchers “don’t have to invoke exotic sexual practices or other means of transmission, such as vaccination,” Hahn said.
At a medical meeting in France in 1990, as well as in more detail at a recent medical meeting in Colorado, Hahn reported the discovery of an HIV-2 sample obtained from the blood of an agricultural worker in the West African nation of Liberia.
This virus is indistinguishable from some samples of the sooty mangabey virus; in other words, it is more closely related to monkey viruses than other human AIDS viruses. Many researchers consider this discovery one of the most compelling pieces of evidence in the search for the origins of AIDS.
One possible ancestor for HIV-1 is a virus that French researchers isolated in 1989 from two chimpanzees in Gabon. There are more similarities between this chimp virus and HIV-1 than between HIV-1 and HIV-2. But researchers are uncertain of the significance of this finding because the occurrence of AIDS-like viruses in chimps in the wild is very rare.
According to Hahn, there are two possibilities. One is that chimpanzees are the source of the ancestor viruses for HIV-1. The second is that there is another primate species that harbors the animal ancestor of HIV-1 and is capable of transmitting the virus to both chimpanzees and humans.
Under either scenario, it is not possible to say when the first humans were infected with AIDS-like viruses. The first human infections might have occurred in this century, or hundreds of years ago among isolated groups unlikely to spread the disease to others.
Also, the earliest AIDS viruses may have been less likely to cause disease than many of their modern-day counterparts, said Hahn and Francine E. McCutchan, an AIDS researcher with the Henry M. Jackson Foundation in Rockville, Md. These early viruses may have had difficulty reproducing. As a result, infected individuals may have remained well and consequently were relatively less infectious to others.
Hahn, McCutchan and others believe that as the virus has adapted to growth in humans, it has become easier to transmit as well as more likely to cause disease.
By this reasoning, it was primarily social changes in Africa after World War II that contributed to the spread of AIDS. These included colonialism’s end, urbanization and increased travel, as well as greater use of needles and blood products. As the AIDS epidemic gathered momentum, increased travel between continents and sexual promiscuity made it only a matter of time before the virus was found throughout the world.
Gerald Myers, director of the human retroviruses and AIDS database at Los Alamos National Laboratory in New Mexico, said accidents may have played a role in transmitting infections. Such accidents, he said, are more likely to have been related to lapses in the sterilization of needles and syringes than to contaminated vaccines or instances in which primate blood may have been injected into humans.
Some humans were injected with blood from chimpanzees and monkeys as part of malaria experiments decades ago, according to a 1991 commentary in Nature, a British scientific journal, which suggested a possible link between these injections and the origins of AIDS. But the number of individuals involved in these experiments was small and it is not known how many of the primates may have been infected with AIDS-like viruses.
By comparison, there are many well-documented instances of the transmission of HIV through contaminated needles and syringes, and among intravenous drug users throughout the world. Lapses in sterilization also appear to have played a role in the case of Dr. David Acer, the HIV-infected Florida dentist who apparently transmitted the virus to some of his patients.
It is not out of the ordinary for humans to acquire a germ that is carried by animals. Cryptococcus, a potentially life-threatening fungal infection for individuals with weakened immunity, most commonly originates in pigeon feces. The infection is believed to be transmitted to humans through airborne droplets. Tularemia, an unusual infectious disease, is typically acquired from rabbits.
Humans have acquired an unusual virus from infected tissues of African green monkeys. This virus, sometimes known as Marburg virus, causes African hemorrhagic fever, an often fatal disease. The virus was named after an outbreak of disease in 1967 among workers at a vaccine manufacturing facility in Marburg, Germany.
There are also instances when a germ enters a new species, then is transmitted within that new species indefinitely. The virus that causes canine distemper, a life-threatening disease affecting dogs and related species, is 95% identical to the human measles virus, said Preston A. Marx, director of the New Mexico Regional Primate Research Laboratory. This suggests that cross-species transmission of the virus might have occurred many centuries ago.
The diseases that a germ causes may vary widely between species. The AIDS-like viruses found in sooty mangabeys do not cause the animals to become ill. But when the mangabey viruses have been transmitted to macaques, another monkey species, a fatal AIDS-like illness has developed. Scientists believe that a similar phenomenon of increased virulence occurred after AIDS viruses were transmitted to humans.
The recent conjectures about the origins of AIDS, such as those involving the polio vaccine, have usually been set forth as theories--not fact. The recent Rolling Stone article noted the geographic and temporal coincidence between the mass trials of an oral polio vaccine in the late 1950s in the Belgian Congo and the center of the African AIDS epidemic.
The article pointed out that the oral polio vaccine was produced in monkey kidney cells, and that some monkey viruses have been known to be transmitted to humans through oral polio vaccines.
The vaccine was developed by Dr. Hilary Koprowski, former director of the Wistar Institute, an independent research facility on the University of Pennsylvania campus in Philadelphia. After the article was published, the Wistar Institute formed a team of researchers to evaluate the theory. They will attempt to locate samples of the original vaccine and test them for AIDS-like viruses.
Scientists have never found AIDS-like viruses in the many polio vaccine batches that have been tested, including the batches mentioned in the Lancet article, said Dr. Gerald Quinnan of the U.S. Food and Drug Administration. Nor is there any evidence that the AIDS virus can grow in monkey kidney cells. Moreover, although the polio virus is spread through the digestive tract, AIDS-like viruses are transmitted by sexual contact, exposure to infected blood and from infected mother to child.
“Polio vaccines haven’t caused AIDS,” Quinnan said. A 1987 report by the World Health Organization reached the same conclusion.
Genetic sequence data on AIDS viruses isolated from around the world has been entered into a data base at Los Alamos National Laboratory. Periodically, researchers have used computers to construct a family tree detailing the relationships of these viruses. The family tree includes viruses isolated from humans as well as those obtained from monkeys and other animals.
The most recent family trees include sequence data on about 40 HIV-1 viruses. The researchers have identified five to six major sub-types of the virus in humans. Some of these sub-types are more common in some parts of the world than others.
“These five to six sub-types appear to have radiated from a similar common ancestor (virus) as recently as 1960,” said Myers, the director of the databank. But Myers and other experts cautioned that this conclusion represents a rough estimate. The strains may have diverged over a far longer period.
The 1960 date is “an extrapolation,” Myers said. “We don’t have a full picture of all this at the moment.”
The earliest human samples showing evidence of HIV-1 date from 1959. They are a blood sample from Zaire, stored as part of a vaccine experiment, and tissues from a British sailor who died of a perplexing immunodeficiency and overwhelming infections. The sailor had visited east African ports.
But the earliest AIDS virus that has been genetically sequenced was contained in a 1976 blood sample from Zaire, Myers said.
In the United States, the earliest suspected AIDS case involved a St. Louis teen-ager who died in 1969. Full molecular characterization of an AIDS virus from this case has not been achieved, nor is it clear how the teen-ager might have been exposed to the virus.
The search for the origin of AIDS is often considered less important than the quest for new AIDS treatments and an AIDS vaccine. But some researchers believe that the epidemic will not be controlled until the origins of AIDS viruses are better understood.
McCutchan, of the Henry M. Jackson Foundation, said the key question is whether cross-species transmission of HIV-1 and related viruses is continuing at a significant rate.
The Origin of the AIDS virus
Here is a simplified family tree showing human and simian immunodeficiency viruses, based on computer-assisted research conducted at the Los Alamos National Laboratory. The researchers believe that the AIDS viruses in humans evolved from related ancestor viruses. The best evidence for this relationship is the detailed analysis of the genetic material of the viruses.
As additional variant viruses are isolated, the family tree of the AIDS-like viruses is likely to change.
A. HIV-1 is the major AIDS virus in humans throughout the world. It has five or six subtypes.
B. So far, a virus isolated from two chimpanzees in Gabon is the closest primate virus to HIV-1. But researchers are not certain that it is the ancestor virus for HIV-1.
C. HIV-2 is a variant AIDS virus common in West Africa. It is closely related to a virus found in the sooty mangabey, a West African monkey.
D. The African Green Monkeys and the mandrill, a West African baboon, also harbor AIDS-like viruses.
