Smallpox is the only human disease that has been globally eradicated through vaccines. It’s also responsible for the first known vaccine, created by the English physician Edward Jenner in 1796. After observing that milkmaids who caught cowpox (a milder disease) seemed to gain immunity to smallpox, Jenner inoculated an eight-year-old boy using a milkmaid’s cowpox lesion. He then exposed the boy to smallpox, and when the boy didn’t develop any symptoms of the deadly disease, Jenner realized he’d developed a way to prevent it.

The experiment, while highly unethical by today’s standards, was a big deal. Smallpox could kill up to 30 percent of people who caught it, and had already killed enormous numbers of Native people in North and South America after European colonists brought smallpox and other new diseases to the continents. Shortly after Jenner developed the vaccine, Spain began using it to inoculate people across its empire. The British soon followed, and in the 1850s, Massachusetts became the first U.S. state to mandate smallpox vaccination.

“By the mid-1900s, right after World War II, countries all around the world decide…‘Why don’t we just get rid of smallpox?’” Najera says. “And so they undertake an effort like no other since or before.” This global effort led to the eradication of smallpox by 1979.

Rabies has played a large role in American film and literature—think Old Yeller, To Kill a Mockingbird and Their Eyes Were Watching God. But the deadly disease, which causes erratic behavior, is no longer a major threat in the United States because of vaccines.

In this case, most of the vaccines that have helped save human lives aren’t used on humans—they’re used on other animals that can carry the disease and infect humans by biting them. State rabies programs have guidelines for vaccinating pets and wildlife and tracking animals that might have rabies. Anyone who is bitten by an animal that has not been vaccinated for rabies, or appears to show symptoms, should go to a doctor or hospital to get checked out and potentially receive a rabies vaccine.

Though rabies is still a threat is some parts of the world, many countries have robust vaccination and tracking programs. “Latin America has one of the best anti-rabies programs in the world,” Najera says. “I got bitten by a rabid dog when I was six years old [in Mexico]. They caught the dog and the dog died a couple of days later from rabies, and so if I would have not gotten the vaccine I probably would have been dead.”

Polio was once one of the most feared childhood diseases in the U.S. The viral infection can cause temporary or permanent paralysis, as it did with wheelchair user Franklin D. Roosevelt. This paralysis could stop a person’s body from breathing on its own, which is why so many infected people had to be placed in an “iron lung.” By the late 1940s, it was disabling more than 35,000 Americans each year. The number of U.S. polio cases peaked in 1952 when it caused 57,879 infections and 3,145 deaths.

During the 1954 trials for Jonas Salk’s polio vaccine, parents flocked to sign their children up to get the shot. As a result, 623,972 children received the vaccine or a placebo. The trials showed the vaccine was 80 to 90 percent effective at preventing polio. Thanks to the continued vaccination of children through today, no polio cases have originated in the United States since 1979. However, polio has not been eradicated and remains a health threat in Afghanistan and Pakistan.

During the early spread of COVID-19, there was a lot of discussion about whether the infectious disease was serious, or “like the flu”—i.e., not a threat. However, influenza remains a deadly disease that has caused previous pandemics and has the potential to cause future ones as well. (Najera speculates the next flu pandemic will happen “sooner rather than later.”)

The Centers for Disease Control and Prevention estimates the flu caused between 12,000 and 61,000 U.S. deaths annually between 2010 and 2020. Globally, it kills between 291,000 and 646,000 people each year.

The deadliest outbreak ever recorded was in 1918 and 1919. That flu pandemic killed roughly 675,000 people in the United States and up to 50 million people worldwide. It also may have infected a third of the world’s population or about 500 million people. Since then, there have been several other flu pandemics.