By Rob Stein
Washington Post Staff Writer
Monday, November 5, 2007
In the decades since young gay men in the United States started dying from a mysterious syndrome in the 1980s, scientists have wondered how and when the AIDS virus arrived. Many scenarios have been proposed, including one early but now-discounted theory that the disease was imported by a promiscuous Canadian flight attendant dubbed "patient zero."
Now, however, scientists reconstructing the genetic evolution of the deadly virus say they have traced its true path -- concluding that the insidious pathogen used Haiti as a steppingstone from Africa to the United States and arrived much earlier than had been thought. It then simmered silently here for more than a decade before it was detected, beginning its global spread along the way.
"This is the first time that we've been able to bring together the geographical picture with the timing picture to show with a pretty high degree of certainty where the virus went from Africa, and when," said Michael Worobey, a professor of ecology and evolutionary biology at the University of Arizona in Tucson, who led the research.
Others praised the detailed genetic analysis of human immunodeficiency virus (HIV) from around the world as an impressive bit of biomedical sleuthing.
"For those of us who have been interested in HIV evolution and the origins of the virus, this is very interesting," said Beatrice H. Hahn, a professor of medicine at the University of Alabama in Birmingham. "It's a very nice piece of work."
In addition to writing a key chapter in the history of the AIDS pandemic, the new insights into the genetic variability of the virus could aid the long-frustrated efforts to develop an effective vaccine.
"What this might tell us is how the virus might evolve molecularly," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. "That might have an impact on the virus that you put in your vaccines. So this not only has historical value but practical implications for vaccine design."
The new work fills in the latest piece of the puzzle of the origins of the AIDS pandemic. Hahn and her colleagues had previously established that HIV originally jumped from chimpanzees to humans, possibly when hunters in Africa butchered animals infected with a version of the virus. In 2000, Bette Korber of Los Alamos National Laboratory and her colleagues found that the virus began to proliferate in Africans around 1930.
But the exact route the virus took as it crept out of Africa before exploding in other parts of the world has been the subject of intense debate and speculation.
"We know that the virus has a deep history in Africa," Worobey said. "I wanted to find out how it emerged from Africa and became the pandemic that we know today."
Worobey started by retrieving six blood samples from cold storage at the federal Centers for Disease Control and Prevention in Atlanta. Arthur E. Pitchenik of the University of Miami had collected them in 1982 and 1983 from Haitian immigrants who had died from a mysterious syndrome, later determined to be AIDS.
"We now know that these are samples from several of the earliest Haitian AIDS patients in the United States," Worobey said.
In the laboratory, his team extracted HIV from five of the samples and analyzed the viral genes. The researchers then compared their findings to molecular sequences stored at Los Alamos of 117 samples of the strain of HIV that is primarily responsible for the global spread of the pandemic outside of Africa. (Other strains, however, account for far more AIDS cases worldwide today.) The researchers used specimens from 19 countries, including the United States, Canada, Haiti and several in Europe, Latin America and parts of Asia, focusing on the diversity of mutations in two key genes.
"Wherever the virus has been circulating the longest, you expect to see the most diversity, because the virus accumulates mutations over time. The longer the virus has been in a place, the more changes you'll see," Worobey said.
Based on the analysis, the researchers reported last week in the Proceedings of the National Academy of Sciences that there is a 99.8 percent certainty that the virus moved first from Africa to Haiti and then leapt to the United States.
Because the mutations accumulate at a predictable rate, the researchers were able to use them as a kind of molecular clock to calculate when the virus arrived in each location. The results indicated that it appeared in Haiti in about 1966 and the United States in about 1969, before traveling to Europe, Canada, Latin America, Australia, Japan and other parts of the world.
"That doesn't mean the virus traveled directly from the U.S. independently to each of those other countries," Worobey said. "It might have gone from the U.S. to Germany and Germany to Estonia and so forth. But once it got into the U.S. population, Americans traveling to other countries and people traveling to America allowed it to flow to other countries. The United States probably served as a worldwide hub for this spread."
The virus may have made its initial jump from Africa to Haiti after the Democratic Republic of Congo won its independence in 1960 and many Haitians sought work there, Worobey speculated.
"There were a lot of Haitian teachers in the Congo. One of those workers may have brought the ancestral subtype B virus back to Haiti. We can't prove that, but it seems plausible. The timing is consistent," he said.
It is unlikely that anyone will be able to identify the individual who first brought the virus to Haiti or the person who took it to the United States, Worobey said.
"Whoever that person was, they had no idea they were carrying the virus, and the person they transmitted it to had no idea," Worobey said. "The chances we'll ever locate a sample from that individual is almost zero."
The findings have raised concern in the U.S. Haitian community that the results could reignite prejudices, but Worobey and others cautioned against assigning blame.
"The idea of blaming groups afflicted by AIDS should be something for the past," Worobey said.
In retrospect, the discovery that HIV arrived in the United States much earlier than anyone knew is not surprising, Worobey and others said. It takes as many as 10 years after infection for most people to get sick, which would have allowed the virus to spread before health authorities became aware of it.
"There likely were individual cases here and there that simply went unnoticed," Fauci said. "You could have had a case in New York and one in Los Angeles or someplace else. Unless you have someone very astute noticing and saying, 'Wow this is unusual' for some reason, no one would realize until they started to see those first clusters."