The world officially became a slightly safer place in October, when the World Health Organization declared that polio’s type 3 strain had been eradicated. This strain — joining type 2, which was eradicated in 2015 — no longer exists anywhere in the world, outside of highly secure laboratories. (Type 1 is the only strain still at large.) Thanks to the hard work of thousands of dedicated individuals, these two strains will no longer cause devastating paralysis or death.

While it was once just a dream, permanently ending diseases has been within our power since 1980, when smallpox was eradicated after an intense campaign. This victory has saved roughly 200 million people who would otherwise have succumbed to the disease since then.

But other attempts to rid the world of diseases have not gone as smoothly. Doctors have been working on ending polio for 31 years, initially hoping it would be completely gone by 2000. Now, due to difficulties tracking the disease, the target eradication date for the remaining type 1 strain is 2023. Another pathogen nearing eradication is a parasite known as Guinea worm, but again, problems have complicated that campaign, and others as well.

So what was it about smallpox that made it so much simpler to eradicate? What makes an organism eradicable in the first place?

Fundamentally, if we want to get rid of a pathogen, we must have a way of stopping its transmission. Halt the spread, and you can isolate those infected without anyone else getting sick. Do a thorough enough job, and there won’t be any new cases anywhere in the world — the disease is eradicated. Theoretically, this process can take many forms. The deployment of an effective vaccine robs a disease of future hosts. Eliminating a key vector takes out the means of infection. And for a bacterial pathogen, antibiotic treatments can target the disease itself. But theory doesn’t always translate to practice in the real world.

For a sense of what actually works, smallpox provides the perfect case study: It turns out to be almost ideally suited to eradication. First, it’s a virus that only affects people, not animals. Wipe it out in humans, and that’s it, you’re done. (We’re not actually sure why smallpox is so choosy, and we’re unlikely to find out anytime soon, since little research today involves the deadly pathogen — and even then, it focuses on treatments and vaccine research over fundamental biology.)

Second, the disease makes its presence clearly and unambiguously known. It produces a rash that’s easy to identify and distinct from rashes caused by other diseases. And infections are not asymptomatic: You can’t be infected and contagious but still appear healthy. (Again, it’s not clear why this is.) These traits make it easier to track new cases and quickly stop outbreaks.

Third, smallpox has a highly effective vaccine, made from a virus closely related to smallpox called the vaccinia virus. Because the vaccine contains a live virus, the immune system produces a rapid, strong and lasting response. The vaccine can even stop a smallpox infection in its tracks. “You can vaccinate somebody who is already developing smallpox up to six days after they have been infected,” said Larry Brilliant, an epidemiologist and former WHO physician who took part in the smallpox eradication campaign. The vaccine made it easier to halt new transmissions and protect healthy people, even if responders arrived at a smallpox outbreak that was already underway.

The fourth reason — and an increasingly relevant one — is not a biological consideration, but a psychological one: Smallpox was a feared disease. People knew it was deadly, and even survivors could be scarred for life. This translated to political support from world governments and local support among populations receiving the vaccination.

All these features in combination enabled us to wipe out one of humanity’s oldest scourges in about a dozen years of intense effort. But if a disease is missing just one or two of these attributes, it can prove much harder to eradicate.

Like smallpox, polio is a disease that only affects humans, and we have an effective vaccine for it. In fact, we have two. But neither is as good as the one for smallpox, and one of them — a live virus vaccine no longer used in the U.S. — has the potential to mutate and cause vaccine-derived polio. In fact, for the last several years, we’ve had more cases of vaccine-derived polio than wild polio infections. (To be clear, no such dangers exist with flu or other typical vaccines.)

Unfortunately, polio differs from smallpox in another crucial way. Approximately 95% of those infected either don’t display any symptoms or only display generic ones such as fever and headache. This means the type of disease tracking that officials used to detect smallpox epidemics is impossible for polio. Instead, health officials take environmental samples to test for polio viruses, with positive results meaning additional vaccine campaigns for the area. The process is repeated until no additional samples contain polio virus. This relatively inefficient approach does work, though, and it’s how we’ve eradicated two of polio’s strains and will hopefully soon take down the third.

Guinea worm is another pathogen whose biology differs enough from smallpox to make it harder, but not impossible, to eradicate. The Guinea worm eradication campaign was championed by former President Jimmy Carter (among others) and launched in 1986, and it has led to a sharp reduction in cases of this water-borne parasite, from around 3.5 million yearly cases to under 30. Like smallpox, Guinea worm provides an obvious and unambiguous sign of infection: After growing in the host’s body for about a year, the worm emerges through the skin through a blister on the lower leg. But Guinea worm eradication has grown more complex over the past five years as doctors have recognized that it’s not a human-specific infection, as had been assumed: Recent studies have demonstrated that dogs, frogs and fish can also transmit the pathogen. This will slow the eradication timeline since the animals can re-contaminate clean water supplies.

But despite these setbacks, the polio and Guinea worm campaigns have shown how viable such goals really are. For future eradication campaigns, yaws and measles are both good potential targets. Yaws is a human-specific infection caused by a spirochete; left untreated, it has the potential to cause serious illness and disability. In 2012, researchers realized that a single dose of antibiotics could treat yaws and break the transmission cycle. Through this method, India became yaws-free in 2016, though the emergence of antibiotic resistance in the spirochete may complicate efforts.

Measles also echoes many of smallpox’s characteristics: It only affects humans, it doesn’t appear asymptomatically, and it has a highly effective vaccine. As a result, worldwide measles deaths have already dropped by approximately 20% since 2000, and the disease has been eliminated in the U.S., meaning it’s no longer constantly present here (despite occasional cases brought in by travelers). But while it’s a good candidate for eradication based solely on its biology, measles doesn’t share smallpox’s crucial psychological factor: People don’t fear it enough. To the contrary, unsubstantiated fears of vaccines are on the rise, harming the global eradication campaign and nearly bringing endemic measles back to the U.S.

So while we may have the biological tools to allow us to eradicate certain diseases, that’s not enough.

“It’s not science, it’s public will,” Brilliant said. “Public will is so critical.”