Here at SciShow, we talk a lot about the fascinating, complicated, and often very weird stories of discovery and collaboration that led to the science we know today.

But one of the strangest is something we haven't covered in much detail before, and it's a biggie: the decades it took to figure out exactly what HIV and AIDS were, and how to prevent and treat them. Since the start of the AIDS crisis, some 70 million people have been infected with HIV, and 35 million of those people have died.

Both those numbers are staggering in their own way, and together, they tell the story of a disease that has led to an incredible amount of loss, but also one that — if you’re lucky enough to have access to the right medicines — is no longer a death sentence. So, in honor of World AIDS Day on December 1, we want to tell you that story. There’s a lot to cover, so we’ll do it in two parts.

This episode, we’ll go over how we figured out what HIV is, when the infection morphs into AIDS, and where we think the virus came from. Next time, we’ll look back to the earliest treatments, the arrival of antiretroviral drugs, which were complete game-changers, and go over the creative ways scientists are now thinking about prevention and possibly even a cure. But first, the basics.

HIV, or human immunodeficiency virus, is a retrovirus that infects immune cells, most notably what are known as CD4 T cells. The “retrovirus” part just means that the virus uses RNA — DNA’s more wily, less stable cousin — as its genetic material, and that once HIV infects a cell, it makes a DNA version of its genome with a special enzyme, then inserts that DNA into the host genome. If that sounds sneaky — well, it is.

And it’s part of why HIV has been so difficult to treat, which we'll talk about more next time. Now, those CD4 T cells that HIV infects and ultimately kills are a kind of white blood cell known as ‘helper’ T cells. When they recognize a threat, they pump out proteins that help coordinate a bunch of different immune responses.

You definitely want them around. HIV is spread by bodily fluids, including blood, semen, vaginal fluid, and breast milk. That’s why HIV can be transmitted through sex, dirty needles, breastfeeding, and any other swapping of fluids you might do — with a major exception: saliva isn’t one of those fluids.

Saliva is full of other stuff that prevents HIV from being infectious, like antibodies and a bunch of antimicrobial proteins. So unless there’s a lot of blood in your saliva for some reason, it can't transmit HIV. When someone is first infected, they might feel like they have a bout of the flu, with a fever, headache, rash, sore throat, and muscle and joint pain.

That’s because the virus is infecting lots of cells and the immune system is trying to fight it off. But within a few weeks those symptoms pass because by then the person has specific antibodies that can keep the virus from running totally rampant. After that, they usually feel fine for a long time — in many cases, a really long time, like several decades.

Until, one day, they don’t, because the virus has finally killed off too many T cells, leaving the body unable to properly defend itself against pathogens — anything that might be dangerous or infectious. That’s when someone is said to have AIDS, or acquired immune deficiency syndrome. Usually AIDS is diagnosed once the person’s T cell count falls below 200 cells per microliter of blood, which is well below the normal 500-1500, or if they develop what's called an opportunistic infection.

These are infections that anyone with a reasonably strong immune system would be able to fight off, easy-peasy. But because HIV has obliterated most of their T cells, AIDS patients get sick. And, they can die.

Most of the time it’s an opportunistic infection that killed them. So, some of that was probably familiar to you, but pretend for a moment that you’ve never heard of HIV or anything else I just mentioned. Because back in the ‘80s, we didn’t know these basic facts.

All doctors knew was that suddenly, healthy young gay men were developing extremely rare infections and cancers — and, it was killing them. One of the first people to notice the pattern was an immunologist at UCLA. Between the fall of 1980 and the following spring, he saw a string of five patients, all gay men in their 20s or 30s, with an unusual kind of pneumonia.

There was a fungus growing inside their lungs. Normally, the fungus was totally harmless and would never infect the lungs, but in these men it had, and it was making it hard for them to breathe. The patients also had oral thrush — basically yeast infections in their mouths — and few CD4 T cells.

By June, when the immunologist wrote up the results for the CDC’s weekly Mortality and Morbidity report, two patients had died. A month later, a dermatologist in New York chimed in with a similarly disturbing report, this time with Kaposi’s sarcoma, a rare cancer where patients develop blotchy purple lesions on their skin. In two and a half years, 26 young gay men in New York and LA had been diagnosed with Kaposi’s.

Some also had the weird fungal pneumonia, and 8 had died. It’s hard to imagine now, but at this point, scientists had no idea what was making people sick. They didn’t know if it was some sort of toxin or a pathogen.

And if it was an infection of some kind, they didn’t know how it was spreading. That meant they couldn’t warn people about how to protect themselves. The association with gay men, though, was certainly striking, and early on, many called the mystery disease GRID, for gay-related immune deficiency.

Lots of people would talk about it as the “gay cancer” or “gay plague.” But the disease wasn’t limited to gay men. It was turning up in hemophiliacs — people whose blood doesn't clot properly and are treated with clotting factors taken from other people’s blood. Doctors were also seeing cases in IV drug users, women, infants, and heterosexual men.

In particular, 20 recent immigrants from Haiti had gotten sick, and none said they were gay. Those clues were important, because they told scientists the disease — which had finally been given the name AIDS — was probably infectious, and probably transmitted by blood. There were other diseases that spread in similar ways, like hepatitis B.

So in March of 1983, the CDC issued a warning that doctors needed to be careful about blood transfusions, and that the disease seemed to spread through both gay and straight sex. Debates about the specifics, including whether it could spread through saliva, would happen later. But what was the infectious agent?

The race was on for scientists to figure out what was causing the disease. French molecular biologist Luc Montagnier suspected a virus because at the time, the blood products hemophiliacs used were filtered for things like bacteria and fungi. But viruses were too small to catch.

So along with his colleague Françoise Barré-Sinoussi, he searched cells taken from AIDS patients and found a retrovirus. Around the same time, Robert Gallo at the NIH in the US also identified a retrovirus in samples from AIDS patients. Both groups published their work in May 1983, and shortly afterward another team found yet another retrovirus.

All the viruses had been given different names, and at first, it’s wasn’t totally obvious that they were the same thing. But they were, and in 1986, the cause of AIDS had been given an official name: HIV. So, HIV was the problem, but where had it come from, and why had the epidemic struck now, in the decade of big hair and Michael Jackson?

While some researchers were scrambling to identify whatever it was that made AIDS infectious, others noticed that macaque monkeys also seemed to suffer from an AIDS-like disease. One group decided to take some blood samples from these sick monkeys, and in 1985 they found a virus that was similar to HIV. It was eventually called SIV, for simian immunodeficiency virus.

Researchers started to think that HIV might have come from our primate relatives, jumping the species barrier. After a lot of work, they figured out that the virus behind the epidemic was very similar to the chimpanzee version of SIV, and they were the ones who had passed it to us. But how exactly?

There’s no real way to put this delicately, but most scientists agree that the reason why SIV made the leap into humans — what’s called a spillover — is because we had a taste for bush meat, or wild game. In this case, monkeys and chimps. This is known as the cut-hunter hypothesis.

In the course of butchering a chimpanzee, some SIV-infected chimp blood enters a small cut on the hunter’s hand. Or, a bit of blood splatters in their mouth. The virus is close enough to human biology to infect the hunter, and over time, if the hunter passes the virus along to enough people, it evolves into the HIV we know today.

Spillovers like these happened many times — we can tell because the virus mutates quickly, and by looking at genetic differences, we can identify multiple lineages of the virus, each one corresponding to a spillover. We’ve traced the current epidemic to just one of these, called ‘M’ for main. By analyzing chimpanzee pee and poop, researchers think the chimps who passed that version of the virus to us lived in southwestern Cameroon, in the forests near the Congo.

And based on the oldest blood samples we can find that we now know have HIV in them, which are from 1959 and 1960, scientists estimate that HIV-1 first infected humans around 1908. If that seems like a long time ago, well, it takes a while for a virus to take off. By the 1920s, it’s thought that the virus traveled downriver — in a person, of course — to the burgeoning city of Kinshasa, then known as the Belgian colonial city of Leopoldville.

There weren’t many women around other than prostitutes, so experts think HIV spread that way, and possibly through injectable drugs the colonists used to treat some tropical and venereal diseases. This was before disposable syringes, and nurses were trying to treat lots of people with just a few of them, so the syringes may have only been rinsed with alcohol before being used on the next patient. So the very methods meant to stop the spread of disease may have actually been encouraging it.

With time, infected people in Kinshasa left to go to other places, and they did the unavoidable: they brought the virus with them. Because the virus mutates so quickly, we can group the viruses into 9 different subtypes and get a sense of how HIV traveled around the world from Central Africa. Several subtypes spread to other parts of Africa.

Subtype C went south and then landed in India. Subtype B went to Haiti — and then, through several quirks of history, came to the US. First, in 1960, when the Belgians left the Congo, French-speaking Haitians started to arrive in the Congo to work as doctors, lawyers, and other professionals.

But with the creation of Zaire in 1965, the immigrants felt unwelcome, so they went back to Haiti, bringing HIV with them. There, HIV expanded especially quickly, possibly because of a plasmapheresis center where people could get paid to donate their blood plasma. The center used a machine that mixed the blood of different donors, allowing viruses to transfer.

By 1982, nearly 8 percent of a group of young mothers in a Port-au-Prince slum were HIV-positive — an astoundingly high number. HIV is thought to have entered the US around 1969, with just one infected person or unit of plasma from Haiti. It took about a decade for anyone to notice, but by then it was too late.

The epidemic had begun, and HIV was not only in the Americas, but Europe and Asia, too. And now that it was here, we needed to figure out how to fight it. But we'll get to that in the next episode of this mini-series.

In the meantime, thanks for watching this episode of SciShow, and if you want to learn more about HIV and all kinds of other science, you can go to youtube.com/scishow and subscribe.