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Rewriting the History of AIDS in America: Exonerating Patient Zero

OCTOBER 26, 2016
I remember vividly when “GRID” (aka HIV/AIDS) was rare, in the early 1980s.

BIRTH OF THE EPIDEMIC

Every Thursday the little white pamphlet would come in the mail, the CDC’s Morbidity and Mortality Weekly Report, the MMWR. Coverage of the new syndrome began a few cases at a time. Otherwise healthy young men were developing the purplish skin blemishes of Kaposi’s sarcoma, a cancer known only in elderly Italian men, or a rare form of pneumonia known to ravage the lungs of those with poor immunity. The patients were men-who-had-sex-with-men (MSM) before that coin was termed, so the mysterious disease became known as gay-related immune deficiency, or GRID.
 
Cases accumulated. People died. And fingers began to point at certain sectors of society seemingly sensitive to the new scourge – MSM, people who received frequent blood transfusions, sex workers, and people from Haiti.
 
A few years later, my eldest daughter Heather would string together those priceless early reports from the CDC to chronicle the rise of the epidemic in a term paper, and receive a bad grade from a teacher oblivious to the value of a primary source. Why no Time or Newsweek? Heather anxiously followed the sad and maddening story of Ryan White, the teen who contracted AIDS from a blood transfusion and catalyzed the fight against discrimination when he and his mother stood up to his school in Kokomo, Indiana, that wouldn’t let him return. I think he contributed to Heather becoming a social worker.
 
My three daughters never knew a time before AIDS.
 
Time and Newsweek eventually began reporting on the new disease. Then in 1987 came Randy Shilts’ book “And the Band Played On,” the author himself infected. It is one of my favorite books, and as narrative nonfiction, relied heavily on names and stories.
 
One such name was Gaëtan Dugas, a young French-Canadian flight attendant. Shilts dubbed him “patient zero” based on a report from 1984 in the American Journal of Medicine that tested the hypothesis that the new infection was spreading through sexual contacts. Here’s what the study found:
 
“Of the first 19 homosexual male AIDS patients reported from southern California, names of sexual partners were obtained for 13. Nine of the 13 patients had sexual contact with one or more AIDS patients within five years of the onset of symptoms. Four of the patients from southern California had contact with a non-Californian AIDS patient, who was also the sexual partner of four AIDS patients from New York City. Ultimately, 40 patients in 10 cities were linked by sexual contact.”
 
I don’t know how Shilts got the name of the “non-Californian AIDS patient” in those days when HIPAA protection was still nearly two decades in the future, but the media ran with it.

ENTER GENOMICS

Back in 1983, researchers in the US and France were still squabbling over who had discovered which virus when. Was the culprit HTLV, HIV, or LAV? President Reagan delayed monitoring of the blood supply. And people kept dying. The idea to sequence a human genome was still about three years away, but the first viral genome had been sequenced in 1977.
 
A paper published today in Nature exonerates Gaëtan Dugas, who was designated patient “O” for “out(side) of California.” Not only was he never patient zero, but HIV had been circulating in the US since the early 1970s.
 
Technical advances made the new work possible, layered onto the rich historical tapestry of connecting the earliest cases by sexual contacts. Michael Worobey from the University of Arizona, Tucson and colleagues developed an approach they call “jackhammering” to take an “early, full-genome snapshot” of the shattered snippets of RNA from archival samples. They reverse transcribed the RNA into DNA, then overlapped the pieces to deduce entire viral sequences – rather than relying on the fragments consulted previously. The strategy sounds a little like putting pieces of tape onto puzzle pieces to help assemble them into a coherent picture.
 
The investigators started with thousands of plasma samples from the 1970s, from men-who-have-sex-with-men who’d participated in clinical studies, many to initially investigate hepatitis B, another sexually-transmitted infection. Before the current study, the only available samples from before 1980 were from Africa.
 
From the thousands of samples the researchers obtained clear genome results from 8 individuals, 3 from San Francisco (the supposed birthplace of HIV/AIDS in the US) and 5 from New York City. These viral genomes are a subset of HIV genomes from the Caribbean, which are more diverse because they’ve been around longer.
 
Comparing genome sequences of viruses is in essence an evolutionary study – like constructing branching tree diagrams to depict how we diverged from other Homo species. Molecular clocks are superimposed on DNA sequence comparisons by considering mutation rates of specific genes and the variability in the gene sequences among individuals – that’s how viral arrivals are linked to specific years. The mantra of evolutionary genetics is that the more alike two DNA sequences, the more recently two individuals shared an ancestor - - or one passed a virus to another.

 FROM AFRICA TO THE CARRIBEAN TO NYC TO SF

The results reveal a very clear picture: “HIV-1 group M” traveled from Africa to the Caribbean in 1967 (plus or minus a few years), then “jumped” from the Caribbean to New York City in 1970, 1971, or 1972, and then from New York City to San Francisco in 1976 – even though the Bay Area is where the CDC tracked down the first US cases. The “jump” from the Dominican Republic, Jamaica, Trinidad, Tobago, and Haiti had to have been in the early 1970s to account for the viral diversity seen in US cases later in the decade.
 
The “ancestral US virus” was from the Big Apple, “strongly suggesting that this was the crucial hub of early US HIV/AIDS diversification,” according to the new report. Once the virus came to the US, the epidemic took off due to the large number of people, with US incidence overtaking that of the Caribbean by 1977. 

Fuzzy diagnoses may have contributed to the 1980s dates for the first cases. For example, the medical records of some men who developed Kaposi’s sarcoma or the pneumonia in the 1980s indicate swollen glands in the mid 1970s. Retrospective diagnosis sets back the epidemic a decade.

 MR. DUGAS DIDN’T START THE AIDS EPIDEMIC

The clash of classic epidemiology from the 1980s with modern genomics is fascinating, brought to light by the posthumous exoneration of the unfortunate Mr. Dugas. He became the center of the 1984 “sociogram” because he blabbed about his partners, naming names and citing cities, fueling an ascertainment bias. He was likely never a literal “patient zero,” much as “mitochondrial Eve” was not a specific individual but a figurative one. However, once Randy Shilts provided a name to fulfill the human need to blame someone for something terrible, the “patient zero” moniker persisted to the extent that it founded a new term in epidemiology.
 
When the researchers resurrected the complete genome sequences from the viral matter still in Mr. Dugas’s plasma sample, they concluded that “we find no evidence that patient zero was the first person infected by this lineage of HIV-1”. According to the evolution written into the viral nucleic acid sequences, his partners were likely already infected.
 
The CDCs numbering of cases during the days of the emerging epidemic, before anyone knew it was an epidemic, was hardly systematic, and didn’t always reflect order of infection. Gaëtan Dugas was in fact patient #57. Records indicate that he was initially called “non-Californian AIDS patient” when he saw a doctor about his unhealing purple skin lesions, which became “out(side)-of-California.” Confusion between the letter “O” and number “zero” may have led to the historical misnomer.
 
The stunning new paper not only revises an important part of medical history, but is a testament to the power of probing the information in genomes – even the tiniest ones.
 


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