Polio, because there’s an effective vaccine for it and because it’s restricted to humans, also looked like a promising target. By 1988, when WHO and a coalition of governments decided to attack it, the disease had been largely banished from Europe and North America. And yet smallpox, fearsome though it was as a killer, was actually easier to eliminate than polio. This is because—unlike smallpox, which struck its victims with visible pustules and scars—polio is largely invisible, making it far more difficult to track and eliminate.

The poliomyelitis virus has likely been living with humans for millennia. Archaeological excavations of prehistoric burial grounds, as well as paintings in ancient Egyptian monuments, show limb paralysis that is probably the result of polio. The virus, part of the enterovirus genus, is extremely contagious and spreads through two routes—oral-oral, through saliva, or more commonly fecal-oral, like when an infected person’s feces contaminate the water supply. In the crowded, unsanitary cities of antiquity and medieval times, this meant that virtually everyone would have been exposed to the virus in childhood. For most people, this wasn’t a problem: The virus typically infects only the mucosal tissues of the gastrointestinal system for a few weeks, where the immune system clears it before any harm is done. After that, the infected person would be immune to future infections from the same strain. However, in less than 1 percent of infections, the virus attacks the central nervous system and causes paralysis. Typically this affects just the legs. But in 5 to 10 percent of paralytic cases (that is, 0.05 percent of total infections), polio paralyzes the breathing muscles, meaning that without artificial respiration the patient will suffocate.

All this explains why polio is so difficult to annihilate. For every one person who actually gets sick, nearly 200 are carrying the virus and infecting others. To detect the spread of the disease in Afghanistan as soon as possible, Zahed and his colleagues have built a network for reporting suspected cases of polio-related paralysis. Since Afghanistan’s public health care system is almost nonexistent in many rural and remote areas, they’ve recruited all sorts of locals to whom parents are likely to bring a sick child: mullahs, shrine keepers, pharmacists, faith healers, and traveling quacks. They’ve been given basic training and are paid a reward of about $5 for reporting a confirmed case of paralytic polio. Moreover, advances in rapid genetic sequencing have allowed researchers to chart the path of each infection, showing the complex and often unexpected ways in which polio can travel.

Despite such advances, though, the invisible nature of most infections means that areas thought to have been cleared can flare up again with little warning. For example, this year tests of sewage in both Israel and Egypt, which had been deemed polio-free, revealed polio virus that was descended from a strain detected in Pakistan—even though no symptomatic cases have yet been reported in either country. To prevent a return of the virus, population immunity levels need to be kept very high—above 90 percent. And every year, a new cohort of unvaccinated children is born. Unless they are vaccinated, a susceptible population can build, ripe for a return of the virus. In Somalia, polio transmission was stopped in 2007, but fighting between Islamist groups and the Western-backed government in recent years has rendered large areas of the country inaccessible to vaccination programs. The polio campaign watched nervously until finally disaster struck with a new outbreak in May, with nearly 200 cases this year, and some reported in Ethiopia, Kenya, and South Sudan as well. In October, who announced that it was investigating a cluster of possible polio cases in Syria, where the conflict has produced more than 2 million refugees.

For all the laurels heaped upon Henderson and the generation of epidemiologists who slew smallpox, eradicating polio may be the hardest initiative that the world public-health community has ever undertaken. Based on the timeline with smallpox, the original vaccination plan in 1988 was that polio would be gone by the turn of the millennium. But in 2000 there were still roughly 700 confirmed cases of polio paralysis worldwide, and the disease remained stubbornly entrenched in Africa and South Asia. Now, 13 years later, the target date has been pushed back to 2018. Reaching that goal depends on the vaccinators who go door to door in the world’s most unstable regions, trying to immunize nearly every child.