Using sophisticated genetic testing techniques, scientists have determined that the AIDS virus that has spread to more than 40 million people worldwide since 1981 got its toehold in humans in the 1940s or early 1950s in central Africa.
The findings, announced Tuesday at a scientific conference, stem from a tiny scrap of HIV found in the blood of a man who lived in Kinshasa, the capital city of Congo in central Africa. The sample was taken from him in 1959.
The work represents a major step forward in the effort to unravel the mystery of how and where the worst epidemic of modern times got started.
“This is, to date, the oldest known HIV case,” said David D. Ho, director of the Aaron Diamond AIDS Research Center at Rockefeller University in New York, who presented the data at the Fifth Conference on Retroviruses and Opportunistic Infections in Chicago.
The findings suggest that all 10 subtypes of HIV-1, the viral type that has fueled the global AIDS epidemic, evolved from a common viral ancestor, which likely jumped from a nonhuman primate to a human some 50 years ago, scientists said.
Scientists still don’t know whether it was a chimp or some other primate that passed the virus on to a human. And they don’t have any answers to the more puzzling question of what might have happened in central Africa to fuel the virus’ spread from one person to another after it entered the human population.
Ho speculated that the virus might have been spread by contaminated needles used in a mass vaccination campaign against other disease or by social changes, such as the construction of roads.
“This is the only bona fide fossil case (of HIV) we have,” said Beatrice Hahn, a virologist at the University of Alabama at Birmingham and an expert on the evolution of HIV. “It may help explain what is actually responsible for the epidemic.”
The research that led to Tuesday’s announcement spans more than 40 years, and provides an object lesson in persistence and the value of unfettered inquiry into basic scientific questions.
It began in 1957 when Arno G. Motulsky, a young geneticist at the University of Washington, began investigating the genetic basis for an inherited blood disorder that is common among people of African origin. He wanted to find out whether the trait, which involves a growth factor deficiency, evolved because it conferred partial resistance to malaria, thereby providing its carriers with a survival advantage.
Motulsky drew 1,213 blood samples from Africans of different origins, including hundreds from what was then known as Belgian Congo. After they were analyzed in his own laboratory, they were sent to a collaborator at Emory University in Atlanta.
In the mid-1980s, shortly after French and American scientists announced their discovery that HIV was the cause of AIDS, the Emory scientist told a colleague that he had a freezer of blood plasma samples drawn from central Africa in the late 1950s.
“I said, ‘Oh, boy,”’ recalled Andre J. Nahmias, an infectious disease specialist at Emory.
Nahmias, who discovered a genital herpes virus, had never worked with HIV. But he knew the blood samples might provide valuable clues about how the AIDS epidemic might have begun.
He was able to confirm the presence of HIV antibodies in just one sample. That sample, labeled only L70, came from a healthy Bantu male in what was then known as Leopoldville, the capital of Belgian Congo. Nothing else was known about the man because of Motulsky followed standard scientific protocol in not identifying test subjects by name.
In 1986, Nahmias published his astonishing finding in the Lancet, a British medical journal. If correct, the blood sample from the Belgian Congo represented the oldest known case of HIV infection.
“One would have thought that people would believe us, but the timing was wrong,” Nahmias recalled.
In the mid-1980s, many governments in Africa were officially denying that AIDS was a problem in their countries, even as the virus was wiping out entire villages.
Nahmias’ work was eclipsed in 1990 when British scientists announced that they had isolated HIV from a 25-year-old sailor who died in 1959 in Manchester, England.
Now scientists were regarding the sailor as the oldest known documented case of HIV infection.
But in 1995, Ho changed all that. Writing in Nature, he reported genetic tests raised “serious doubts” about the authenticity of the Manchester sailor as the first documented case of AIDS. Tests indicated that his tissue samples had been contaminated with HIV of more recent origin than 1959.
Nahmias asked Ho if he would like to perform the same sophisticated genetic tests on his Leopoldville sample.
Using a technique called polymerase chain reaction, or PCR, Ho’s team, which included researchers at the Los Alamos National Laboratory in New Mexico and the University of Nottingham in England, took a tiny piece of viral RNA and amplified it so scientists could study the sequence of its genes.
The amount of material was infinitesimal - four short sequences of just two of the nine genes that make up HIV.
But by comparing it to existing sequences for the different subtypes of HIV-1 around the world, the scientists were able to find the probable place of the viral sample on the HIV family tree.
The findings suggest that the man in central Africa was infected with an HIV that was close to the center of the HIV-1 family tree. It was almost certainly an ancestor to subtype B, now the dominant strain in North America, and subtype D, one of the dominant strains in Africa, Ho said.
For Nahmias, the finding represents a vindication. His main hope, he said, is that the new findings assist researchers in tracking down how the virus jumped from a primate to a human.
“That’s now the missing link,” he said.
And in Seattle, where he is still a medical geneticist at the University of Washington School of Medicine, Motulsky is marveling at the findings stemming from a single vial of blood he collected as part of a different research project almost four decades ago.
“I may be the first person who drew blood from an HIV positive person,” he said.
xxxx EARLIEST HIV The oldest specimen of HIV was found in blood collected in 1959 from an adult Bantu man in what is now the Democratic Republic of Congo. Comparison of its genetic material to current strains suggests that HIV first crossed from monkeys to humans shortly after World War II, according to Dr. Tuofo Zhu of the University of Washington.