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Jad Abumrad: Hey, I'm Jad Abumrad.
Robert Krulwich: I'm Robert Krulwich.
Jad: This is Radiolab and today-
Robert: It's Patient Zero. That's our subject.
Jad: Yes, and this next story--
Robert: It's so huge.
Jad: It's the ultimate Patient Zero story, really.
Robert: Many of us have lived through this. It's as recent an event, it's such a recent event that it still hurts and it still bleeds.
Robert: In it somewhere is literally the patient that is called Zero.
Jad: Yes, and a lot of people are going to help us tell this story, but starting us off is science writer, Radiolab regular Carl Zimmer.
Carl Zimmer: In 1981, doctors for the first time, describe-
Newscaster: A mysterious, newly discovered disease-
Carl: -a syndrome.
Newscaster: -which affects mostly homosexual men.
Carl: The young men in Los Angeles-
Jad: -were dying.
Newscaster: The number of cases has been growing faster and faster.
Newscaster: So far more than 80 Americans have died.
Newscaster: 258 people have died.
Newscaster: 625 people have died.
Jad: Of course, this is the part we all know, how from those first few cases in LA, AIDS became one of the deadliest pandemics the world has ever seen.
Newscaster: More dangerous than the plague of the middle ages.
Jad: But back at the beginning, there was a story that I have not been able to shake for the last 30 years, and it's a story that I want to reimagine right now.
David Quammen: Right after news of this syndrome started to break.
Jad: That science writer David Quammen, who, along with Carl, will be one of our guides.
Carl: Epidemiologists were trying to figure out where-
Newscaster: Where did it come from?
Carl: And they were thinking like, "Well, maybe it's a sexually transmitted disease."
Jad: The CDC launches a study-
David: -of a group of about 30 patients-
Jad: -gay men-
David: -in New York, Los Angeles, and San Francisco to see who had had sexual contact with whom.
Jad: Is that just a series of interviews with people?
Carl: Yes, please name all the people that you've slept with.
Jad: The CDC eventually releases the results of this survey in the form of a diagram.
David: Like a network drawing, with circles representing patients and then lines representing sexual contact.
Jad: And each patient, each little circle was numbered.
David: New York, 7. Los Angeles, 12.
Jad: So you didn't know who was who, but you could tell immediately when you look at this thing, that of all the 30 or so circles, there was one circle that was special. It had lines coming out in every direction.
David: Seven or eight emanating from him.
Jad: Like the hub of a wheel, except all the spokes on this wheel, connected to other wheels, which then shot out and connected to other wheels, fanning outward. At the center of it all was that one little circle numbered-
David: -Zero, number zero.
Jad: As far as we know, that was the first time that you ever get the term Patient Zero.
Newscaster: Patient Zero was a man, the central victim and victimizer.
Jad: This is from a 60 minutes special in 1988. That year a reporter named Randy Shilts had written a book called, And the Band Played On, that for the first time revealed the identity of Patient Zero.
Newscaster: He was a French Canadian-
Newscaster: A very handsome airline steward.
Newscaster: Named Gaëtan Dugas.
David: Gaëtan Dugas.
Newscaster: Patient Zero.
Jad: A few minutes later in the report, Shilts comes on to describe a guy.
Randy Shilts: A guy who has got unlimited sexual stamina.
Jad: This sexual athlete, who would fly from one hotspot to the next, because of his job, having sex with literally thousands of men.
David: And as he knew he was dying, at least according to Randy Shilts, he became somewhat sinister and malicious. He would sleep with a male partner at a bathhouse in San Francisco or somewhere else, and then when the light came up, according to Randy Shilts, he would say, "I've got gay cancer."
Selma Dritz: Now, you're going to get it too.
Newscaster: You talked to him.
Selma: I talked to him, yes.
Jad: This is Dr. Selma Dritz. She was part of that CDC study.
Selma: I told him that he was getting other people sick with it and he said, "It's my right to do whatever I want. My civil right. I do as I please. I've got it, why shouldn't they have it?" They said, "You can kill yourself if you want, but did you got no right to take somebody else along with you." He said, "Screw you," and walked out.
David: Really a chilling moment.
Jad: Pretty much from that moment on, Gaëtan Dugas-
Carl: -he just took on this aura as single-handedly causing an epidemic in the United States.
Jad: Now, I don't know about you but I first bumped into this story in the movie version of And the Band Played On.
Movie clip: My friend, we're talking about thousands of men whose faces I cannot even remember and you want names.
Jad: That's an actor playing Gaëtan Dugas movie. Now, when I first saw that, AIDS had already infected two and a half million people, and to think that it could all go back to this one guy just seemed unreal.
Carl: It was a very potent story, there's no doubt. He gave HIV to a lot of people. There's no question about that. What we do know is that he was not Patient Zero.
Jad: He was not Patient Zero.
David: He was not the beginning point.
Carl: He wasn't.
Jad: Not even close. Here's the question that got me started on this story. The Gay Steward, that was the movie stuck in my head but what's the real movie? What movie can we make about the beginning of the AIDS epidemic? When you've got something so vast that according to some estimates will have killed 60 million people by the end of the decade, well, you need a beginning. You need some way of explaining how this disaster happened and how it might happen again?
Robert: How exactly do we know that Gaëtan Dugas wasn't Patient Zero?
Carl: Well, there are a couple of reasons we know it. One thing that people started to do-
Carl: -was to-- they then started going back and looking at people who had died-
David: -people who died mysteriously-
Carl: -of AIDS-like things-
Jad: -in the past.
David: Might some of them have been early cases?
Carl: They started finding a lot.
Newscaster: Robert Rayford had AIDS 12 years before it was recognized in this country in 1981.
Newscaster: In 1959 a sailor in Britain died of pneumocystis pneumonia.
Jad: For a while, you had all these new Patient Zeros.
Newscaster: In 1961, a nurse in Chicago died of Kaposi's sarcoma.
Carl: The real definitive blow to this so Patient Zero nonsense came by actually looking at the virus itself.
Jad: In 1984, same year that Gaëtan Dugas died, scientists isolate the virus.
Jad: Which is really just a little string of genetic code that gets into your body and then into your cells and uses your cells to make copies of itself. Here's the thing.
David: When it replicates within a single patient, it copies itself imprecisely. It mutates quickly. It changes a lot.
Jad: As the virus duplicates itself inside a person, the dupes often have little copying errors in them, little mutations. It turns out those errors, they happen at a predictable rate. You can almost predict how many you're going to see in a year or five years. The amount of changes that you see out there, the diversity really of the viruses in the AIDS population, well, that becomes really good information. A group of scientists began to look at-
David: -the amount of diversity among HIV patients in the US-
Carl: -and other parts of the world.
Robert: The more diversity, the longer the virus has been around.
Jad: Right, right.
Carl: They could use that like a clock. If you have a virus here and a virus there-
Jad: You could measure how different they are and you would know that it would take a certain amount of time for them to get that different. To make a long story short.
Carl: The picture they get is-
Jad: -that AIDS entered the United States-
Carl: -around 1966-
David: -at a time when Gaëtan Dugas was still a virginal adolescent.
Jad: From there, scientists were able to trace the virus back to Haiti. From Haiti, back to Africa.
Michael: It's been there the longest. It's had the longest time to become diverse, to mutate, to evolve. If you want to get to the real Patient Zero as it were, the most interesting stuff actually comes from Africa. One way to try to figure out its origins there is to go looking for the virus.
David: Yes. That takes us back to ZR59 and DRC60. Can we talk about them?
Jad: Sure. What?
David: These are the two earliest known HIV-positive human specimens.
Jad: This is where for me at least the story gets way bigger than I imagined. Now the first sample.
Jad: Came to light in the late '90s. Somehow scientists unearthed a very old tube of blood from a hospital in Kinshasa in the Democratic Republic of Congo. When they tested it-
David: It had HIV. This had been taken from a Bantu man in 1959.
David: Yes, nobody knows his name. Nobody even knows I think what he died of. That was the only one for a number of years.
Michael Worobey: That was our one glimpse into the deep history of HIV.
Jad: Then along comes that guy, Michael Worobey. He's an evolutionary biologist at the University of Arizona. A few years ago, Michael went back to Kinshasa and found a second HIV sample. He actually found the virus lurking in a tiny bit of human tissue that was preserved in paraffin wax.
Michael: It's like Han Solo in the Star Wars movie when he's frozen in that carbonite, or whatever that stuff is.
Jad: This new sample, it was from the same town, Kinshasa, as the first and also, more importantly, from the same time.
Michael: 1960. With the two of them, then you can go back in time.
Jad: Like we described before, you can measure the differences between the samples, calculate how long it would take for those samples to get that different. In the end, you can use these two samples to wind the clock all the way back to the virus that started it all. It turned out-
Michael: -the most recent common ancestor of those two specimens-
Jad: -goes back to-
Michael: -to about 1908.
Jad: 1908. That is when it started in human beings.
Robert: What, 1908? Is that what you're saying?
Michael: -give or take a margin of error.
Carl: Early 1900s.
Jad: Around 1908, give or take, something happened.
David: That's right, that moment is the spillover.
David: Spillover is the term the scientists use to describe the moment when a virus in one species passes into another species.
Michael: New diseases in humans tend to pop up from animals. People said, "Okay, flu comes from birds. Where does HIV come from?" To get at that answer, you have to look beyond human beings. You have to look at other viruses that are like HIV.
Robert: So the search was on.
Newscaster: The inability to find a similar disease in research animal-
Jad: Turns out right about the time that the HIV virus was discovered-
Newscaster: What scientists at the New England Primate Research Center--
Jad: Some researchers found a virus like it in macaque monkeys. In fact, it was so similar that they called it-
David: Simian Immunodeficiency Virus.
Beatrice Hahn: Yes. That's where the origin quest started.
Jad: This is Beatrice Hahn.
Beatrice: I'm a professor of medicine and microbiology at the University of Pennsylvania.
Jad: After they found it in macaques, what happened?
Beatrice: It took a couple of years-
Jad: -but eventually, she says, they found SIV-
Beatrice: -in still another primate species, the sooty mangabey.
Jad: Then in a few more.
Beatrice: African green monkeys, mandrills.
Jad: Pretty soon it was all over the place.
Beatrice: There are now, I think, 40 different species of African monkeys known to have their own version of SIV.
Jad: Then the question was, "Which one of these monkeys or primates passed it to us?"
Beatrice: Then unexpectedly-
Jad: -a researcher named Martine-
Beatrice: Martine Peeters.
David: -at the center in Gabon-
Jad: -decided to test her chimps.
Beatrice: Two orphaned chimpanzees-
David: -and Bingo, she found a very, very close match.
Beatrice: A virus that was the closest relative of HIV one. Everybody said, "Well-
David: It was a chimp.
Robert: It was a chimp.
David: Yes, it came from chimp.
Jad: Then the question was, Well, which chimps or rather, where?
David: "Where exactly?" Beatrice Hahn and her colleagues started looking at chimps that came from different parts of western Central Africa.
Jad: Now, getting blood samples from chimps in the wild is pretty much--
Beatrice: It just isn't feasible.
Jad: Because in the wild, they hide the moment they see us.
Beatrice: You get stuck with fecal samples.
Beatrice: Yes, poop.
Carl: There's lots of DNA in there.
Jad: And viruses.
Carl: They would just go to where the chimpanzees would sleep at night and they would just collect some poop.
Jad: Bring it back to the lab and Beatrice would analyze all the viruses.
Beatrice: Over 90 different wild communities-
Jad: -from every part of Central Africa.
Beatrice: Over 7000 different fecal samples.
Jad: Slowly they were able to piece together-
Beatrice: -which communities were infected and which ones had the closest to HIV one. That's when it hit us for the first time.
Jad: What exactly hit you?
Beatrice: The geographic origin of these chimps.
Jad: In 2006, her and her colleagues published that the human AIDS virus comes from a group of chimps, a very specific group that live in a very specific place.
Michael: This little corner of southeastern Cameroon.
Beatrice: Between the Boumba River, Ngoko River, and the Sangha river.
Jad: These chimps were essentially penned in between these three rivers.
Michael: Scenario probably only of 100 square miles, not much more than that.
Robert: When we're looking at what humans have, and we're looking at what all of those chimps in Africa have, the most perfect match is this little territory up there in Cameroon.
Beatrice: There is no other virus that is any closer. That's that.
Jad: Can you reconstruct the spillover and the who that it spilled over into as best as you can understand it?
Michael: You can hypothesize, and the best hypothesis is the "Cut Hunter" hypothesis.
Jad: The "Cut Hunter."
Robert: The C-U-T Hunter?
Michael: That's right, a hunter who gets cut.
Jad: What can we say about this guy? What do we know about him?
Michael: If we had to guess, that human was probably a Bantu man living very near the forest or in the forest in southeastern Cameroon. He was hunting. Maybe he had a bow and arrow, maybe he had a spear and he kills the chimpanzee. Bingo. Here's a big pile of meat, and he starts to butcher it. He's cutting open the chest cavity, he's pulling out organs, and he cuts himself and he gets blood to blood contact. Chimpanzee blood against his blood.
What happens is that the virus in the chimpanzee blood found itself in an environment that was unexpected, that was alien to it, but was not too much different from the biochemical environment it had been in, chimpanzee blood. It could function and that's the moment, that's the moment it begins. That human is Patient Zero.
Jad: But why then? Why 1908? I mean, presumably, people have been hunting chimps for a really long time. Why wouldn't this guy be patient seven million?
Michael: That's another of the big questions. People certainly in Central Africa have been eating monkeys for thousands of years.
Jad: David says, there's really no way to know but this could have just been the right virus.
David: Maybe this particular virus evolved in a way that made it more transmissible in humans.
Jad: Or maybe it just got lucky to come along at precisely the right time.
Carl: What you're looking at-
Jad: This is Carl, again.
Carl: -is at a time when this part of Africa was being heavily colonized. The French and the Belgians were building train systems and the populations were on the move. Kinshasa, which was then Léopoldville, it was exploding. It was huge.
David: The cities were attracting people from the boonies in those days.
Jad: By 1908, all the virus has to do, is get from that tiny village where the cut hunter lived to one of the new cities.
David: That happens almost certainly, by river. I was stirred by the work of Beatrice Hahn and Michael Worobey to see what this scenario looked like on the ground. I went to southeastern Cameroon and I chartered a little boat, about a 30-foot wooden boat with an outboard motor-
Jad: -and he traced the path of the virus.
David: We went down the Ngoko River and we stopped at a few villages. There are a couple of little villages there, one of which has a market where you can buy monkey meat and crocodile meat.
Jad: He says, it wasn't hard to imagine how it all might have went down. Perhaps the cut hunter gave the virus to a woman, who then passed it on to a fisherman-
David: a fellow that I called the Voyager-
Jad: -who then got in a boat, as David did, and carried it down the river.
David: The Sangha River, which is the-- the Ngoko was a tributary of the Sangha. Sangha becomes a bigger river, 200 meters wide, which then flows to the Congo River, the big river-
Jad: -and into the city.
David: I imagined him sliding into Brazzaville around 1920, the first HIV positive man to arrive in an urban center, where there's a much greater density of humans, where there are prostitutes, a greater fluidity of social and sexual interactions. That seems to have been the place from which the disease went global.
Robert: That's how it happened?
Jad: We could take it back even farther, actually.
Robert: What do you mean?
Jad: Well, because if you want to make a movie about the start of it, well, this is not the start. Because we got it from chimps, right?
Jad: You could ask, who was Chimp Zero? What do we know about Chimp Zero?
Michael: Yes. I mean, everything comes from somewhere, and again, by molecular work, scientists have been able to determine that the chimp virus is actually-
Jad: -it actually comes from-
Michael: -two monkey viruses.
Jad: Two different monkeys, from two completely different species.
Robert: What? Would they have encountered each other somewhere and had a fight or?
Michael: They probably encountered each other in the stomach of a chimp.
Robert: Meaning what?
Nathan Wolfe: Well, from the perspective of a chimpanzee, monkeys, they look tasty.
Jad: This is Nathan Wolfe.
Nathan: Professor in human biology at Stanford University.
Jad: He says to fully understand this part of the Patient or rather Chimp Zero narrative, you have to grasp how it is that chimps hunt and this is something he witnessed-
Nathan: -in the Kibale National Forest, in southwestern Uganda.
Jad: He described to us watching three male chimps converge on a tree full of colobus monkeys, which are these very small black and white monkeys.
Nathan: One individual managed to grab two juveniles. Then the three individuals all met up and-
Jad: -began to eat the monkey while it was still alive.
Nathan: The chimpanzee was going after an organ, that obviously was a tasty morsel that he was going after. The monkey was screaming bloody murder.
Jad: It is quite disturbing to watch, he says.
Nathan: But one of the things that struck me at that moment was the depth of contact between the blood and body fluids of this monkey and the chimpanzee.
Jad: The chimps are literally covered in blood. They have blood on their face, in their eyes. From the virus's perspective, this is spillover heaven. The following is the closest that we can get to a zero point in this entire narrative. We don't know where it happened-
Nathan: -and we don't know exactly the time, say some hundreds of thousands of years ago.
Jad: From the molecular clock, we know it was less than a million years, that's all we know. Whenever it was, Chimp Zero was hunting and it comes upon a monkey called a red-capped mangabey.
Nathan: The red-capped mangabey, this is a larger primate.
Jad: These are tree-dwelling little guys?
Jad: A little bit of red fur on their heads.
Jad: Chimp Zero spots one of these monkeys, eats it. In the process, he catches a red-capped mangabey version of the AIDS virus. Next, sometime after that first kill, weeks, months, we don't know maybe it was the same day, Chimp Zero comes across another monkey. This monkey was called a spot-nosed guenon.
Jad: It's got a spot on its nose, I assume.
Nathan: There you go.
Jad: Very small.
Nathan: One of the tiniest monkeys of all of the old world monkeys-
Jad: -and Chimp Zero eats that monkey, and gets a spot-nosed guenon version of the AIDS virus or the SIV virus inside it.
Nathan: You've got the red-capped mangabey and you've got the spot-nosed guenon. You've got a guenon and a mangabey.
Jad: Two completely different kinds of SIV viruses inside the same chimp. Now, under normal circumstances, according to Nathan, both of these SIV viruses would go nowhere because-
Nathan: When one of these viruses makes the jump-
Jad: -they go from a place they've adapted to and that they know to a completely foreign landscape.
Nathan: Like a human being dropped off on Mars, maybe without a spacesuit. They basically are entering a completely alien habitat. The cells don't look the same. The environment is different-
Jad: -and the chimp’s immune system would normally kill them.
Nathan: But then once in a blue moon-
Jad: -something crazy happens. These two viruses will end up inside the same cell in the same chimp at the same time.
Nathan: Literally, there is a single cell simultaneously infected with both viruses.
Jad: Suppose on one side of the cell you've got the mangabey virus, and on the other side of the same cell you've got the spot-nosed guenon virus.
Nathan: What happens is, literally-
Jad: -inside the cell-
Nathan: -you have an enzyme, it's called the polymerase enzyme, that's copying genetic information of the viruses.
Jad: This is what viruses do. They hijack these enzymes to make copies of themselves. Now, here's the problem.
Nathan: These enzymes, they're not necessarily that sticky.
Jad: While they're in the process of copying one virus-
Nathan: -every once in a while-
Jad: -they'll accidentally fall off. Make a copy and go drop and latch on to the second virus and just keep on copying. What it ends up spitting out is a hybrid. Like that. Now, this new mosaic probably won't go anywhere because 99.99999999% of the time when these hybrids happen-
Nathan: -it's a dead-end.
Jad: The chimp's immune system is pretty sophisticated. It has evolved defenses against these viruses and it will destroy them. But again, once in a blue moon-
Nathan: This is a blue moon after a blue moon after a blue moon to really get this. Finally, you get one particular mosaic virus, between the mangabey and the guenon-
Jad: -that through sheer random luck, works. It landed on the exact right combination of genes that allowed it to evade the chimp's immune system.
Nathan: One of the amazing things to think about is, how many hopeful monsters you had to have in order to get that one that actually survived.
Jad: Probably trillions, but then-
Jad: Suddenly in a flash from these two viruses that can barely survive in the chimp, you get a new virus-
Nathan: -a little bit mangabey, little bit guenon
Jad: -that can not only survive in the chimp, but can thrive. In fact, for this baby virus, the chimp is the perfect host.
Nathan: That was the virus that ended up spreading, jumping over into humans, and has been this massive and incredibly dramatic tear in the fabric of humanity.
David: Let me add another parenthesis. There are essentially 12 major groups of the HIV virus.
Jad: What David means is that 12 different kinds of HIV viruses have spilled over 12 different times.
David: Eight of them came from monkeys, three of them came from chimps, and one came from gorillas.
David: Of those 12, only one of them is responsible for the global pandemic.
Jad: There are 12 kinds.
David: 12 times that we know about. It's probably happened dozens and dozens more times that we don't know about. The spillover is not a highly improbable event.
Nathan: These sorts of viruses, they're constantly pinging at us. They're pinging at us and pinging it at us. We see it happening all the time.
Jad: You see it happening?
Nathan: All the time.
Jad: Nathan has set up a series of monitoring stations-
Nathan: -in places like central Africa-
Jad: -and he and his colleagues have been tracking what he calls the viral chatter in the people who hunt these primates.
Nathan: We collected specimens from the animals that they were hunting.
Jad: They compared that to blood samples from the hunters themselves.
Nathan: Guess what? We found a whole range of new retroviruses that were moving over into these haunters.
Jad: For example, he's been tracking something called the Simian foamy virus, which is-
Nathan: -a virus in the same family as HIV.
Jad: He has seen it hop from an individual gorilla to an individual human who killed that gorilla.
Nathan: Yes, these are almost certainly what we call primary transmission events.
Jad: Oh, so you really are looking at the potential beginning of something.
Nathan: Yes. If you want a Patient Zero, really clear Patient Zero, it's some of these individuals that have been affected with these viruses. The real question is, how do we stop Patient Zeros? How do we avoid Patient-
Jad: -Patient One and Patient Two.
Jad: Nathan is developing a series of tools, like-
Nathan: -digital surveillance. Some of these places, I work in some places in Democratic Republic of the Congo, you basically have to fly in to get there.
Jad: No roads. Often no electricity, but-
Nathan: -many of these places, they still have cell phone towers.
Jad: Nathan has begun to track cell phone call patterns in these communities. If he sees a blip of many calls to a medical center within a short period of time-
Nathan: -okay, boom, now we've got to investigate that. We continue to find viruses that are completely novel, and we're looking to determine if these are the next HIV.
Jad: Because thinking about it, he says, HIV landed in humans in 1908, but we didn't know about it until 1981.
Nathan: We had decades of time when this was a virus before it spread globally.
Jad: What if we'd been looking for it?A lot of people to thank for this segment. Thanks to Nathan Wolfe-
Robert: -for being Nathan.
Jad: He has an awesome new book called The Viral Storm.
Robert: Also thank you to Carl Zimmer, whose book on viruses is called A Planet of Viruses, and thank you also to him and to Michael Worobey. Their interview was recorded on a podcast for Meet the Scientist, which you can find at microworld.org.
Jad: Thanks to David Quammen who's got a book called, Spillover coming out very soon, which is all about diseases crossing over from animals to us.
Robert: Also to Beatrice Hahn at the University of Pennsylvania.
Jad: And to Katie Slocum from the University of York for letting us use her recordings of chimpanzees.
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