AIDS Virus Mystery - the missing link

[Ninotchka]

Mystery of an Epidemic's Origin
Gina Kolata New York Times Service

Linking Humans and Chimpanzees to the AIDS Virus

NEW YORK Three years ago, Beatrice Hahn got a call from a colleague asking if she wanted some body parts from a chimpanzee that had died a decade ago. The colleague said, "I have the spleen, the brain and the lymph nodes in my freezer. I need to clean my freezer, so before I throw it out, do you want to look at it?"

Then the scientist said the animal had antibodies in its blood very much like ones that people develop when they are infected with the AIDS virus.

Dr. Hahn leaped at the chance. It was a long shot, but it was possible that the long-dead chimpanzee could be a missing link in the search for the origins of AIDS. A few days later, a huge box of frozen chimpanzee body parts, packed in dry ice, was delivered to her laboratory at the University of Alabama at Birmingham, where she is a professor of medicine.

That chimpanzee, which had been healthy until she died in childbirth at age 26, held clues that eventually enabled Dr. Hahn and an international group of 11 others to unravel the mystery of the origin of the epidemic. Some said AIDS was caused by a mutant virus, a sort of Andromeda strain. Others favored conspiracy theories suggesting that HIV had been created by scientists and escaped from germ warfare labs. Then there was a more pedestrian idea - that people got HIV from primates in Africa.

Scientists tended to favor the primate hypothesis because they knew that diseases can jump from animals to people. Dengue fever, Hantavirus, influenza and hepatitis B all originated in other species. But, researchers learned, it was not easy to trace the virus causing the human AIDS epidemic, HIV-1, to an animal.

The first evidence that HIV-1 jumped to humans from primates came about a decade ago, when scientists isolated a virus from an African chimpanzee that closely resembled the AIDS virus now infecting tens of millions of people. The chimpanzee virus looked so much like HIV-1 that it was almost irresistible to think that the animals had somehow given the virus to people. Adding to the evidence was a tantalizing snippet of another AIDS-like virus found in a tube of blood from a baby chimp that had died.

A few years ago, scientists found a third chimpanzee with an AIDS-like virus, but when they analyzed that virus, they discovered that it was only distantly related to HIV-1. So, were chimpanzees the source of the human AIDS epidemic? Or were chimpanzees, and humans, becoming infected by some other animals?

That was when Dr. Hahn examined the frozen chimpanzee organs, and the mystery began to crack. That animal, she discovered, also had a virus in its tissues that looked like HIV-1.

Suddenly, said Edward Holmes, an evolutionary biologist at Oxford University in England, he and others who had questioned whether chimpanzees really were the source of HIV-1 in humans, became convinced. While scientists had found only two, or possibly three chimpanzees that had the virus, Dr. Hahn's information added to three other lines of evidence, was enough.

One line of evidence pointed to west-central Africa as the place where the human AIDS epidemic began. Scientists, analyzing the genetic sequences of AIDS viruses in patients from around the world, were discovering that the viruses in west-central Africa were the most diverse. And it is a general rule that the more diverse an organism's genes are, the longer it has been around. For example, Mr. Holmes said, human DNA is most diverse in Africa, supporting the idea that the human species originated on that continent.

The second line of evidence was a plausible way for the virus to get from chimpanzees to humans. People in west-central Africa eat chimpanzees. It was entirely reasonable to think that an infected animal's blood gave the virus to a person who was handling the chimpanzee meat, infecting the person and setting the stage for an AIDS epidemic.

Finally, researchers were discovering AIDS-like viruses in other animals and other primates in Africa, but none was as closely related to HIV-1 as the viruses in the three chimpanzees. The only species that fit all the evidence as the source of HIV-1 was the chimpanzee, Mr. Holmes said. A scientific paper that Dr. Hahn had published about the frozen chimpanzee "was extraordinarily important," Mr. Holmes said. "It really made people believe that chimps were the ancestral species."

Paul Sharp, a professor of genetics at the University of Nottingham who worked on the analyses of the viruses, said: "It had been a gradual shift in our perceptions. At first we had been saying that either chimps are the source or they are recipients, like humans." Dr. Hahn's chimp made all the difference, he said.

Now, researchers say, they have found two more chimpanzees that were infected in the wild with a virus like HIV-1. The animals were among a group of 29 captured in Cameroon, in the west-central region of Africa.

Knowing the virus came from chimpanzees left two pressing questions. When did the virus take hold in the human population? And how?

Bette Korber, a molecular geneticist at Los Alamos National Laboratory in New Mexico, and her colleagues had the genetic sequences of viruses isolated from people and knew when those viruses were found, starting with the oldest human HIV sample available. It was from a man from Kinshasa, now the Congo, in west-central Africa, in 1959. Since the viruses mutate at a roughly constant rate, the researchers could construct a path of how the virus had mutated and determine how long it would take to move from one virus to another with the amount of genetic diversity found today. From those calculations, they found a date when the epidemic was ignited: 1931, plus or minus 15 years.

"You might think, if the virus was present in 1930, how on earth did we not see it?" she said. "But if it is only present in a few thousand individuals and it takes a decade to get sick, it could easily have been missed."

Researchers say the virus almost certainly infected humans repeatedly as they killed and ate chimpanzees over the years, but that it is hard to start an epidemic. For it to develop, the virus must be prevented from dying with its victims and a steady chain of transmissions must occur.

"We think that these transmissions have gone on forever and a day, for all the centuries that people hunted chimpanzees," Dr. Hahn said. "The rule is that these transmissions go nowhere. They just peter out, unless you have additional factors that promote subsequent spread in the new human host."

One possible explanation for the extensive spread of HIV-1, several scientists said, was that people began congregating in cities in Africa. There, the conditions were ripe for an epidemic.

Another possible explanation is scarier. Ms. Korber asked if it was possible that nothing really special made the epidemic grow, other than an initial transmission that, by chance, did not die out. Could a very slow curve of exponential growth, starting around 1930, end up in an epidemic that finally caught the world's attention around 20 years ago?

That model is particularly troubling, Dr. Hahn said.

"If you say, 'I don't know how it got started; it could have been this, it could have been that,' and if all you need are a certain set of circumstances in the beginning so that it doesn't die out, then it could happen again," she said.

"People don't want to hear that."