The Dallas Morning News - Monday, February 22, 1999
Laura Beil

The search for the ancestry of the AIDS epidemic has led scientists to the belly of Africa, to the exact region where the first known victim of the pandemic lived and died. The origin of AIDS, chronicled just this month, suggests that a chimpanzee virus slipped into the human population sometime this century. Then, the infection may have churned silently like a warming kettle of water, until finally boiling over in the late 1970s.

But for scientists, the new chimpanzee finding is just as much a beginning as an end. Although researchers may have the best evidence so far that AIDS came from chimpanzees, no one can yet say how the virus became lethal to humans, and when. Also, disease detectives are still investigating how, after taking root in just a few people, AIDS gradually sent shoots all over the world.

Knowing the epidemic's history satisfies more than academic curiosity. The past behavior of the disease may provide a glimpse of the future that can help the development of a vaccine and guide prevention efforts.

For example, researchers now believe that AIDS-like viruses jumped from chimp to human more than once, creating different strains of the human immunodeficiency virus. That means a vaccine against one strain of HIV may not control a new epidemic, said Dr. Preston Marx of the Aaron Diamond AIDS Research Center and Tulane University Medical Center in New Orleans.

"Unless we get to the source and stop new strains from emerging, we could have a long and continuing struggle," he said.

The discovery may also provide clues that could guide scientists searching for a cure. Chimpanzees share more than 98 percent of the genes that exist in humans, yet they don't get AIDS. So which of the remaining genes protect chimpanzees from an infection that has turned out to be almost universally fatal in people?

Long before the chimpanzee connection was known, scientists suspected that the AIDS virus had a close cousin in African primates. Those conclusions are based in part on similarities between HIV and SIV, the simian immunodeficiency virus. But many kinds of primates harbor SIV. For almost 20 years, no one could tell which animal - and which natural SIV host - was the grandfather of AIDS.

"I think now we know that it is the chimp," Dr. Beatrice Hahn of the University of Alabama at Birmingham said in Chicago during the Sixth Conference on Retroviruses and Opportunistic Infections.

Dr. Hahn's investigations focused on HIV-1, one of two types of AIDS virus. HIV-1 is the virus that is responsible for most of the world's current 30 million human infections.

Dr. Marx has helped trace the origin of HIV-2, an AIDS virus that hasn't spread with the vigor of HIV-1. For the most part, HIV-2 has remained confined to western Africa.

HIV-2 came from another primate, the sooty mangabey monkey. In fact, researchers have found one strain of HIV-2 that is more closely related to sooty mangabey SIV than it is to other HIV-2 strains.

Dr. Marx and his colleagues found the origin of HIV-2 by taking blood samples from monkeys and people in the areas where HIV-2 circulates in the population. In this part of Africa, sooty mangabey adults are often killed for food, and the hunters will bring home the orphans for household pets.

Researchers then analyzed the genetic makeup of the monkey and human viruses.

"Those in the pets most closely matched the HIV-2 in the population," said Dr. Marx, who published his findings in the Journal of Virology in 1996 and 1997.

Genetic analysis also led researchers to one particular subspecies of chimpanzee. Dr. Hahn and her colleagues examined four chimpanzees known to have natural infections with SIV. One of the four was infected with a form of SIV so different from the others, and so unlike HIV, that researchers had doubted that chimpanzee SIV could have been responsible for AIDS.

But the scientists then learned that the fourth chimpanzee, the one whose SIV was so distinctive, belonged to a different subspecies from the others. Three of the four belonged to a subspecies called Pan troglodytes troglodytes. Further research concluded that HIV-1 appeared to be related only to the SIV infecting that subspecies.

As it turned out, Pan troglodytes troglodytes lives in the region of Africa where HIV-1 was first recognized. Since there are three separate kinds of HIV-1, the scientists believe that HIV-1 crossed into people from chimps at least three times.

Further confirmation of the work has come from French scientist Francois Simon of Bichat Hospital in Paris, who is analyzing unpublished data from three more animals. All were Pan troglodytes troglodytes naturally infected with SIV that appears closely related to HIV-1.

What is needed to prove the link?

"More chimps," Dr. Simon said.

These may be increasingly difficult to find. The subspecies has been hunted to the edge of extinction, and roads that now cut through the rainforest have made the hunting much easier.

SIV appears to have dwelled in primates for hundreds of thousands of years before turning into a deadly human virus, Dr. Hahn said. She believes hunting, which exposes people to excessive amounts of blood during slaughter, allowed SIV to infect humans.

The emergence of AIDS should serve as a warning about other encroachments into the depths of the rainforest, Dr. Marx said.

"If HIV is adapting to form new epidemics, what else is out there?" he said. "We're creating situations where new viruses can emerge."

The work on neither HIV-1 nor HIV-2 can pinpoint exactly when SIV leapt from chimps to humans, or how.

Scientists do have some idea when the virus began to circulate among people, however. From looking at samples of virus taken at different times and different parts of the world, researchers have constructed a sort of genetic clock for HIV-1. The speed of the clock is determined by how much the virus changes over time.

"This can give us estimates of the age of the epidemic," said Dr. Steven Wolinsky of Northwestern University Medical School in Chicago.

A key to setting this clock came with the discovery of the oldest known HIV-1 infection, that of a man who lived in what is now Congo in 1959. That year, he had been one of 1,200 Africans who had given a blood sample as part of a study of the immune system. After the AIDS epidemic began, the frozen samples were thawed and screened.

By comparing HIV-1 samples taken over time, Dr. Wolinsky and his colleagues have determined that AIDS began to spread within decades before the 1959 sample was drawn. The estimate is based on the assumption that the rate of change for HIV has remained about the same.

Studies have also indicated that HIV-2 began to spread about the same time, Dr. Marx said.

"Never before in thousands of years of exposure to SIV did these viruses cross over to cause [widespread] disease in people," Dr. Marx said. "And yet it happened twice this century. . . . Not only did this happen in chimpanzees, it happened in sooty mangabeys 1,000 miles away."

Many scientists have speculated about why the virus might have become amplified in post-World War II Africa. Among the possibilities: the exploding population of urban centers; social upheaval and commerce that led to migration across the continent; and widespread vaccination campaigns that could have reused needles. In the end, HIV's early accomplices aren't known for sure.

Nor is it clear how AIDS came to the United States, one of the first countries where the condition was recognized. The earliest known case occurred in St. Louis in 1968, in a 15-year-old boy who was admitted to St. Louis City Hospital with symptoms now known to be hallmarks of AIDS complications. The case has remained puzzling. The youth reportedly never traveled outside the Midwest, researchers reported, although they suspected he had been a prostitute.

In the early 1980s, when the epidemic was evident only among Haitians, North Americans and Africans, many reports and news stories questioned whether the disease had come to the United States from Africa via Haiti. Being Haitian was even considered a risk factor in itself, a label that led to the stigmatization of an entire nation. It now appears, however, that Americans probably brought the virus to Haiti, said Dr. Jean William Pape, who treated his country's first AIDS cases.

After completing training in infectious disease at Cornell University Medical College in New York, Dr. Pape returned to Haiti in 1979, on the brink of the epidemic. The initial scientific reports, which described rare diseases in gay men in California, would appear in 1981.

"Our first patients had contact with American homosexuals," said Dr. Pape, director of GHESKIO, a Haitian AIDS research group. During the 1970s, he said, Haiti became a favorite vacation spot for gay travelers, and his early patients lived or worked in the tourist centers.

Through extensive studies of these patients, and of Haitians who immigrated to Central Africa for political reasons in the 1960s, he and his colleagues could find no connections to AIDS in Central Africa, he said. Autopsy records among hospital patients in Haiti also did not contain any mention of distinctive AIDS complications, such as the skin cancer Kaposi's sarcoma, before 1978.

Dr. Pape says he did not undertake his research to somehow deflect blame from Haiti. There should be no blame, he said, because no one is responsible for a disease that now touches almost every place on Earth.

"I think that we've passed this period of stigmatization," Dr. Pape said. "We should move beyond that. We just all need to work to make it a better world."

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