Be Smart

- For years, the story of how AIDS reached America pointed to this man, a handsome airline flight attendant who crossed the country city after city, and, according to the headlines, knowingly spread a death sentence to countless people igniting an epidemic.

They called him Patient Zero.

This story shaped how the world viewed AIDS.

It stoked fear and persecution.

Here's the problem.

It's not true.

Decades of molecular detective work has untangled the truth about how HIV and AIDS first surfaced and how it spread around the world.

Scientists took apart the story of Patient Zero, gene by gene, to reveal the secret life of a virus that starts a century earlier on another continent with a hunter, a chimpanzee, and a drop of blood.

(bright pensive music) Hey, smart people.

Joe here.

The story of AIDS, or at least our understanding of it, begins on July 3rd, 1981 in Los Angeles where Dr.

Michael Gottlieb was working as an immunologist and physician.

- In 1981, I was the first author on the first report that described AIDS as a new disease.

- [Joe] Beginning in late 1980 in Los Angeles, Gottlieb began seeing patients, all young men, with unusual infections, things like pneumocystis pneumonia.

It's a fungal infection of the lungs that you don't normally see in young people or people with healthy immune systems.

- And that kind of gave us the idea that they might be immune deficient.

We saw one patient and then another and then a third patient.

- So on June 5th, 1981, Gottlieb sounded the alarm by publishing a short, urgent writeup in the CDC's weekly bulletin.

He was already convinced that those cases were not a coincidence.

They were the start of something.

- People tell me that they remember where they were when they read that report.

Three cases something very strange, very weird.

Three cases turn up as a tipping point.

- Soon after, doctors in New York City began to see a spike in cases of this rare skin cancer among homosexual men.

Like Gottlieb's patients, these lesions were being triggered by an infection, but it was an infection almost never seen in young people with healthy immune systems.

Something very weird was going on here.

Now the patients were all shown to have low numbers of this particular type of white blood cell.

Now this type of cell is crucial to how the immune system normally responds to infection.

Without these cells, the immune system weakens and it allows rare and weird infections to wreak havoc on the body.

Soon after studying samples from the sick patients, researchers in the US and France found the likely culprit, a newly identified virus, one that behaved in very strange ways and was never before seen in humans.

That virus was HIV.

Just so we're clear, the collection of symptoms that Gottlieb was seeing, that's called AIDS, and that HIV is the virus that causes that disease.

And understand everything that comes next and how we solve this mystery of where HIV came from.

Well, I need to tell you how this virus works because this thing is freaking weird, scientifically speaking anyway.

Now, almost everything I'm about to tell you about this virus those first doctors didn't know yet.

We learned all of this later, but it explains everything that Gottlieb was seeing.

Now this virus doesn't attack the body directly.

Your immune system is this big coordinated machine with a lot of moving parts.

(pensive music) Like any good army, it has a general, one type of cell that reads what's happening and tells everybody else what to do.

And that is a type of white blood cell called a CD4 T cell.

A healthy person carries somewhere around a thousand of these CD4 cells in one drop of blood.

Doctors call it AIDS once that number falls below 200.

This virus hunts the one cell that tells every other immune cell what to do.

It's a classic military strategy, decapitate the chain of command.

It doesn't go after your lungs or your skin or your blood directly.

It searches for that master coordinator of your immune system.

It latches onto this docking point on the surface, like a lock and key, and then it slips inside.

Here is the strange part.

(dramatic music) When the virus gets into one of your cells, it can splice a copy of itself directly into your DNA, into your own genetic code, and then it could just go quiet, sit there doing nothing invisible to your immune system for years until one day it flips the switch, it decimates your immune system and something that should never hurt you, like a common little infection, becomes a death sentence.

That's what AIDS is.

Not one disease.

It's a total immune system collapse.

But how does a virus pull off something that's sneaky?

Well, to understand that, you got to look at how it's actually built.

HIV is what's known as a retrovirus.

(laidback retro music) The instructions for all of the havoc that it's about to wreak in the body are written in just about 9,000 letters of RNA.

- It's over 9,000.

(grunts) - For comparison, our genome is something like six billion letters.

And of course, ours is made of DNA, not RNA.

For something this devastating, the virus has got an almost insultingly small genetic toolkit.

It's just around nine genes and they make just 15 proteins.

A few of them just build the basic machine, the shell, the enzymes that copy it and sneak it into your genome.

But the rest, those are these special little gadgets, tiny tools for picking locks and, as we'll see, for disarming the traps that your cells set for invaders.

The most important is this one.

It's an enzyme called reverse transcriptase.

Now most life on earth runs in one direction.

Your DNA gets read out into RNA.

The RNA builds the proteins that run the show.

DNA to RNA to you.

HIV uses reverse transcriptase to run this backwards, RNA to DNA.

Then it basically hot glues itself right into your genome.

That is how it hides.

Thing is, when it does that cool little trick, it copies itself with the precision of a photocopier that's been kicked down the stairs.

It has no spell check.

It makes a lot of mistakes.

And that is an important detail because later it's going to crack this entire case wide open.

So that's our suspect, this backwards-running virus that hides inside your own DNA, copies itself badly on purpose and carries these tiny tools for picking the locks on your immune system.

Which raises the only question that really matters, where did something that's weird come from and when?

Because a virus this strange didn't come from nowhere.

It turns out HIV has a family, a big one.

And its closest relatives, they don't live in people at all.

- AIDS, as a disease, had popped out totally out of the blue.

And no one really understood where it was coming from.

And for a long time, people did not know what was causing it.

- Well, scattered across Africa, there's this whole group of similar viruses that live in primates, monkeys and apes.

We call them SIVs, simian immunodeficiency viruses.

They're HIV's cousins.

Dozens of ape and monkey species carry their own version.

When scientists lined up the human virus against these primate ones, the matches were uncomfortably close.

- And when all the sequences at the time were put into one family tree, and so it was clear just looking at that picture, that family tree picture, that the two human AIDS viruses had two different sources in two different primates.

- [Joe] One version of the human virus, HIV-2, turned out to be the near twin of a virus carried by a monkey called the sooty mangabey.

It lives in West Africa.

That HIV-1, that's the version of the virus behind the pandemic.

It matched a virus in chimpanzees.

- And that is when we decided to use non-invasive methods to screen chimpanzees all over Sub-Saharan Africa.

At the end, we had about 20,000 samples spanning the entire waterfront, and we were able to detect virus in the wild.

And we found an area in Cameroon that had, where chimes lived wild, who had viruses that were super closely related to HIV-1.

So we think it's that part of Cameroon where HIV-1 group M came from.

The main group, the pandemic group.

- So HIV didn't come from nowhere.

It didn't fall out of the sky.

And despite what you may have heard, it didn't come out of a lab.

It's a primate virus.

It crossed over from other animals into us.

The obvious question is, how does that even happen?

(pensive music) What's even weirder?

We think this crossing didn't happen just once.

It happened over and over and over again.

So if a chimp virus has been getting into people again and again for who knows how long, why isn't the world drowning in like a dozen different HIV pandemics?

Why did just one of them explode?

And the answer is almost every time that a virus like this tries to jump species, it fails.

And to understand why, we need to build a family tree.

This is HIV-1.

It's the virus behind the AIDS pandemic worldwide.

But there's also HIV-2 over here.

It's pretty much limited to West Africa.

You can think of these two like distant relatives.

Somewhere back in their family tree, they have a common ancestor, but they've had time to mutate and become pretty different.

They're kind of doing their own thing now.

Now let's zoom in on HIV-1, the pandemic one.

When scientists compared the genetic sequences of a bunch of HIV-1 viruses out in the population, letter by letter, turns out these fall into four big groups.

We've got M, that stands for major.

About 90% of folks with HIV have group M. Then there's groups N, O, and P. You can think of all these like cousins, closer related than these, but still different enough.

There's a whole bunch of different subtypes under these two.

We can think of them as like siblings, not as different as the cousins, but not identical either.

So when scientists compared all these HIV-1 cousins here, they got a surprise.

Each of these represent a separate jump into humans from chimps and from gorillas.

That jump happened four different times just for HIV-1.

- And we could show that the transmission occurred actually twice from chimps to humans, one resulting in the M group or the main group with a pandemic group of HIV-1, and the other one resulting in what is called group N. But chimpanzees also transmitted to gorilla one time.

And gorillas then transmitted twice to humans, generating group O and group P.

- But here's the wild part.

Three of those basically went nowhere.

Group N, maybe a few dozen cases ever.

Group P, like a handful of people total.

Group O spread a little bit more, but still stayed mostly in one corner of West Africa.

And then there's group M. Group M is responsible for almost every HIV infection on Earth.

We're talking more than 85 million infections.

It's the same kind of virus, same kind of jump, but the story played out way differently.

So what made M special?

Why did this one take off?

The answer starts with your cells.

Over millions of years, they've evolved their own sort of security system, a set of proteins that exist specifically to wreck invading viruses.

But one of them will shred a virus's genetic code into garbage.

There's this other one called tethering.

It literally grabs new virus particles as they try to leave the cell and tethers them to the surface so they can't escape.

It's like putting the virus in handcuffs.

But the virus has evolved its own counter weapons, and one basically picks the lock on those handcuffs.

- And tether end is one of the molecules that sort of holds it on the cell.

And you need to counteract that in order to get off.

In the evolutionary process, HIV-1 has learned to do this better.

- And to take off in a brand new host, a virus has to have the right counter weapons that work on that new host.

- Don't think these transmissions are easy.

They're not.

Every species including us have innate immune mechanisms to prevent that.

These viruses had to jump through several hoops in order to get to a human and be able to infect that human and be human-to-human transmitted.

The precursor of the M group, you know, had to jump through a little bit fewer hoops than the other ones.

- Group M, it seems, made its jump into humans with just the right weapons, thanks to evolutionary luck and the fact that it had been living in chimpanzees.

Those are apes that we're really closely related to.

It had what it needed to slip past human defenses and spread from one person to the next.

Which raises the obvious and slightly uncomfortable question, how does a virus that lives in a chimpanzee end up in a human in the first place?

- Because this is not an infection like flu that you get by breathing in air.

It has to be contact with infected blood or body fluids.

That's how you get SIVs transmitted from chimps or gorillas to humans.

- Our best idea of how this happened is sometimes called the cut hunter hypothesis.

For a very long time in parts of Central Africa, people have hunted and butchered wild apes and monkeys for meat.

And when you butcher an animal, sometimes you're going to cut yourself.

All it takes is one slip of the knife and the hunter's blood and the animal's blood meeting for just a second.

That's it.

That's the whole event.

That gives the virus like this one the chance to jump between species.

One cut on one hunter's hand touches the blood of one ape that was carrying this one lucky version of a virus, or unlucky, I guess, depending on how you look at it.

But just because a virus jumps into one person, that's not enough to spark a pandemic.

You need one more thing, a world ready to spread that virus.

- Because even if you have a virus that's uniquely adapted to humans, you get infected and you, you know, transmit it to close contacts, but you live in an isolated village and it doesn't go any further, virus is dead, infection is dead.

So you need to have opportunity for onward transmission.

- Which takes us to a boom town about a hundred years ago.

When you trace Group M's family tree all the way back to its root, it points to one place at one moment in time.

And it's not where many people might guess.

It's not some remote village deep in the jungle.

It's a city.

(pensive music) Leopoldville was a fast-growing colonial city in Central Africa.

Today known as Kinshasa, the capital of the Democratic Republic of the Congo.

And the moment in time that our trail points to where pandemic HIV first jumped into humans is right around the 1920s.

That's like 60 years before those cases in Los Angeles that first brought it to the world's attention.

So the question becomes what was it about this one city, this one moment that turned a quiet little virus into the start of a pandemic?

The answer is basically a perfect storm.

Colonial Central Africa was experiencing total social and political upheaval.

Men were being pulled into cities for labor, and that left these boom towns that had far more men than women, which reshaped the local sex trade, because remember, HIV is often transmitted through sex.

And at the same time, the colonial powers were building railways, roads, river steamers, letting massive numbers of people move between these towns for the first time.

And finally, in that era, people were getting injections to treat various diseases.

They were often reusing needles that were barely cleaned between patients.

So this all leads to this horrifyingly efficient way to move a bloodborne virus from person to person.

- If you can think of a perfect way to adapt a virus to a new species, that would be one way to do it.

- So this virus and its lucky little toolkit suddenly had crowds and travel and brand new ways to jump from one bloodstream to the next faster than ever.

The virus didn't change the world.

The world changed around the virus.

And for the next several decades, HIV spreads slowly, invisibly, killing people whose deaths got blamed on something else.

A few years ago, scientists looked at HIV viruses that were uncovered in old blood and tissue samples.

And it turns out by the 1960s there's already so many genetic variants of the virus in Kinshasa alone that it must have been quietly circulating there for decades.

So for roughly half a century, HIV was already out there in secret and no one even realized it.

Which brings us to the part of this story that honestly sounds impossible.

Everything that I just told you, the chimpanzee, the city, when the virus first jumped into humans, I mean, how on earth could scientists possibly know any of this?

You can't, like, interview a virus from 1920, but it turns out you can read its life story.

So remember when I told you to remember that HIV is really super bad at copying itself?

How it makes a genetic typo basically every time the virus makes another one of itself?

That flaw is what solved this mystery.

Every time the virus copies itself and makes a typo, that typo gets passed down to all of its descendants.

And then they make new typos of their own, which get passed down again, mistakes piling on top of mistakes, generation after generation.

So if you take two HIV samples from two different people and line up their genetic code, you can count the differences.

And because the typos accumulate at a pretty steady rate, that count can act as a clock.

The more differences between two viruses, the longer ago they split from a shared ancestor.

This is the molecular clock.

I think this is one of the most beautiful things that we've ever figured out in all of biology.

I mean, the virus's greatest weakness, the fact that it's terrible at copying itself, is the exact thing that lets us figure out its history.

But for the clock to work, to turn, you know, this many mutations into this many years, you need an old sample from a known date to calibrate everything against.

Where do you think you're going to get that?

Like it's just sitting in a freezer in Africa somewhere?

Well, actually, yes, that's exactly where.

The first was a blood sample drawn in Kinshasa in 1959.

The second was pulled from a lymph node that somebody had removed in that same city in 1960, preserved in wax in some forgotten medical archive.

I mean, that's crazy.

We've got a little piece of human tissue from 1960 sitting in a drawer and inside it was the genetic ghost of this virus.

We know how long ago that was.

We can see how many mutations it has compared to other Group M HIVs from other years.

And that's how we know that HIV didn't jump into humans in the 1980s or the 1970s.

That jump happened way, way earlier in the 1920s.

There's a name for this kind of work.

We're digging genetic fossils out of old tissue: paleovirology.

And that is a very cool thing to have on your business card.

Once you've got a working clock, you can actually do more than just put a date on the virus.

You can actually watch where it traveled and when.

Today we know that the trail runs out of Central Africa and across the ocean to the Caribbean.

During the chaos of Congo's independence around 1960, the virus most likely traveled with a person to Haiti where it found a new foothold.

And from there, it jumps from Haiti to New York City right around 1970.

1970, New York.

The virus was already in America, already spreading a full decade before anyone had ever heard this name.

So how did a flight attendant become the villain?

Patient Zero.

Where did that even come from?

(dramatic music) Well, you are not going to believe it.

You might even be compelled to slap your forehead.

It might even make you a little angry.

In the early days of the AIDS epidemic in North America, investigators at the CDC were trying to map how early AIDS cases were connected to each other.

Who knew who?

Standard epidemiology stuff.

Gaetan Dugas was one of the people that they interviewed.

Turns out because he traveled and could recall a lot of his contacts and romantic partners, a disproportionate number of early cases were linked to him.

So in that study, Dugas lived outside California.

So they tagged his case with the letter O. The letter O for Outside California.

Can you see where this is going?

They used typewriters to type case reports back then.

And on a typewriter, a capital letter O and the number zero are basically identical.

Somewhere along the way, Patient O got read as Patient 0.

(bass drum thumping) A typo.

Then a journalist named Randy Shilts put that phrase, Patient Zero, the center of a best-selling book, this book.

The press absolutely ran with it.

"The man who gave us AIDS."

We love a nice clean story with a good villain.

And it was exactly the kind of thing that a frightened public wanted to hear.

There was just one problem.

It wasn't true.

(glass shatters) (cat snarls) - It isn't just one person you put your finger on and say, "This is the person who started all this."

Nor is there any particular good reason to do it that way.

And of course it wasn't true.

- Later, scientists actually sequenced the HIV virus from Dugas' own samples, and they compared it to HIV samples that were circulating in America in the 1970s.

And he's not at the root of the tree.

He's in the middle.

HIV was already spreading and mutating across the country before he could possibly have been the source.

Gaetan Dugas was not the origin of HIV in America.

And I think it's worth asking ourselves why that lie stuck so hard for so long because it tells us something kind of uncomfortable about ourselves.

When people are scared, we go looking for someone to blame and it's almost always an outsider, someone who is already on the margins.

Dugas was gay, he was foreign.

He was an easy target.

We did the same thing to a cook named Mary Mallon in the early 1900s.

Typhoid Mary, an immigrant linked to several cases of this scary disease which was not her fault.

We blamed them because we were afraid and they were an easy target.

You know, that reflex, that rush to find a villain, the desire for a simple story has done a lot of damage over the years.

We've learned a great deal since we first recognized AIDS as a disease in that California hospital.

We've learned that the group M virus came to us from chimpanzees.

We've learned that chimpanzees got it from other kinds of monkeys that they hunt as prey.

We even know that chimpanzees somehow gave it to gorillas.

And it was gorillas that then gave us two of those groups that fizzled out, groups O and P. And we now know that this virus makes our closest relatives sick too.

- The very first wild chimp that we discovered was in Gombe National Park and was one of Jim Goodall's chimps.

And that was super lucky for us because they had known these chimps for decades, research that had been going on there for four decades.

At the time, the dogma was these viruses are not pathogenic in primates.

This is a human thing.

Then we found that one of their communities in the south, Col-on-de community had a catastrophic population decline.

And guess what?

Their SIVcpz prevalence was through the roof.

And we looked at, you know, infant mortality, infants born to infected mothers, and bingo.

And we also learned this virus is pathogenic and it came a little bit as a surprise to all of us because we had just simply assumed it wasn't.

- This is a lesson that we are part of nature too, sometimes in kind of frightening ways.

The entire global catastrophe of HIV traces back to one animal virus making one successful jump into one person.

That's it, one cut on one hunter's hand somewhere around a century ago.

And from that single moment, more than 80 million people infected and somewhere around 40 million dead.

That is how thin the line is.

This isn't ancient history.

People are still exposed to non-human viruses today through the same kind of contact.

- Now I'm sure humans have acquired these types of viruses before.

We just don't see it because they didn't become pandemic.

So I think this is happening at a low rate at all times.

And then you see it when something catastrophic happens.

- And there are hundreds of viruses still undiscovered.

And so we shouldn't rest easy that we've seen the last of these spillover events.

- And the bigger forces that made HIV and AIDS possible, humans pushing deeper into wild habitats, packing into cities, moving around the globe faster than ever.

We haven't slowed any of that down.

That's the same recipe that gave us Ebola, SARS, COVID-19.

In fact, if you think about it, every germ that affects humans today from flu and smallpox to polio or the common cold, they must have come from somewhere else, from something else.

Maybe that's the real lesson here.

The easy story and the true story are almost never the same story.

But the true one, if you're patient enough, if you're curious enough to actually chase it down, gives you something much better.

Stay curious.