It took more than a decade for scientists to develop a single-shot vaccine that worked to fend off measles without causing high fevers and rashes.

Then health officials had to convince people to use it.

Until the vaccine’s debut in 1963, many considered measles, which still killed 500 Americans a year and hospitalized 48,000, an inevitable childhood disease that everyone had to suffer through.

“Measles was such a common disease and its mortality was comparatively low,” says Graham Mooney, an associate professor at the Johns Hopkins Institute of the History of Medicine. “People had more problems than measles.”

One of the earliest accounts of measles comes from a Persian doctor named Rhazes in the 9th century, but it wasn’t until 1757 that Scottish doctor Francis Home discovered it was caused by a pathogen and first attempted to make a vaccine. By then, measles was a worldwide killer.

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An 1822 illustration depicting the symptoms from measles.

“It’s an ancient disease, but it really became globally important with increased global explorations from the 16th century on,” says Mooney. As the most contagious disease humans had ever faced, measles was virtually guaranteed after exposure.

Deaths were greatest in populations with no immunity, such as island nations. An 1875 outbreak in Fiji wiped out up to a third of the population in four months, and Hawaii’s first outbreak in 1848 similarly killed up to a third of the population, just two decades later the king and queen contracted it and died on a trip to England.

Though mortality rates eventually began falling, epidemics could still be devastating. In 1916, 12,000 people died of measles, and three out of four deaths were children under 5 years old. But that same year, a pair of French doctors found measles antibodies in patients’ blood. They showed how the antibodies could protect others from developing the disease, laying the groundwork for developing a vaccine.

By the 1950s, measles deaths had dropped to only 400 to 500 a year, thanks to the availability of antibiotics and improvements in sanitation, medical supportive care and nutrition, says Paul Offit, chief of division of infectious diseases at Children's Hospital of Philadelphia and director of their Vaccine Education Center. (Though antibiotics couldn’t treat a viral illness, bacterial pneumonia was one of measles’ deadliest complications.)

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A lab technician looking for vaccine against measles at New York University Medical Center, circa 1960s.

Nearly Everyone Once Got the Measles

Still, nearly everyone got it. The disease led to an estimated 48,000 hospitalizations a year from complications such as ear infections, croup, diarrhea and pneumonia. About 1,000 children a year developed encephalitis, brain swelling that could cause intellectual disability or death.

Among those parents left reeling from the death of their children from the disease was children’s author Roald Dahl, who watched his daughter die from measles encephalitis in 1962. He would later dedicate his book, The BFG, to his daughter’s memory.

Even surviving a measles infection didn’t end your risk of death: a very rare, fatal complication called subacute sclerosing panencephalitis (SSPE) could develop one to two decades later, causing gradual deterioration until the person entered a coma and eventually died.

John Enders
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Dr. John Enders, 1955.

A measles vaccine would lighten a huge public health burden, and scientist John Enders at Boston Children’s Hospital was determined to make one.

'Now this will hurt a little. Are you game?'

When a measles outbreak hit a boys’ boarding school about 45 minutes outside Boston in January 1954, Enders sent one of his researchers, Thomas Peebles, to collect blood samples. Peebles drew blood from infected boys, telling each one, “Young man, you are standing on the frontiers of science. We are trying to grow this virus for the first time. If we do, your name will go into our scientific report of the discovery. Now this will hurt a little. Are you game?”

First Measles Vaccine Was 'Toxic as Hell'

Within a month, Peebles had isolated the virus from the blood of 13-year-old David Edmonston. By 1958, the Boston Children’s team had a live virus measles vaccine to test in disabled children institutionalized at Fernald School and Willowbrook State School, where close living quarters increased infection risk during outbreaks.

Maurice Hilleman
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Dr. Maurice Hilleman, 1957.

But the virus in the vaccine wasn’t weak enough: Most children developed high fevers and rashes similar to mild measles. Enders then shared the strain with other scientists, including Maurice Hilleman, the top Merck scientist responsible for developing more vaccines than any other person in history.

“It was toxic as hell,” Hilleman told Offit, a protege of Hilleman, who recounted the conversation in his biography of Hilleman. “Some children had fevers so high that they had seizures.”

After turning to other experts, researchers came up with a way to grow the vaccine safely in eggs and give the vaccine with a simultaneous shot of measles antibodies to reduce side effects. By March 21, 1963, the FDA licensed the first live virus measles vaccine, Merck’s Rubeovax.

Other measles vaccines were soon approved, including an inactivated (non-live) one that same month with fewer side effects but less protection. It was pulled from the market in 1968, the same year Hilleman refined the vaccine into the one used today—one without the severe side effects and which didn’t require the extra shot of measles antibodies.

By then, measles cases had dropped by 90 percent, and the CDC had already declared a plan to eliminate measles two years earlier. The next step was persuading parents to immunize their children.

Measles vaccine
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As part of the national immunization effort, this doctor was giving a measles vaccination to a young boy at Fernbank School in Atlanta, Georgia, 1962.

School Vaccine Rules Lead to Measles Elimination

“Public apathy in the face of infectious disease has always been a problem for public health,” Mooney says. The problem wasn’t the hesitancy seen today so much as complacency.

“It was a case of parents prioritizing getting food in their kids mouths than vaccinating them against measles,” particularly among poorer Americans, Mooney says. It cost parents about $10 ($82 today) to vaccinate one child against measles. The Vaccination Assistance Act in 1965 provided funds for measles immunization, but the money ran out in the 1970s, contributing to an upsurge in cases.

“Many mothers simply have not been educated about the benefits of and need for immunization,” noted the New York State Department of Health in 1971. That same year, Hilleman combined measles, mumps and rubella vaccines into a single MMR shot to cut down kids’ total jabs.

But it wasn’t until widespread school vaccination requirements and permanent federal funding that the country began inching toward measles elimination, finally achieved in 2000. (While cases of measles still crop up, the Centers for Disease Control defines elimination of a disease as the absence of continuous disease transmission for 12 months or more in a specific geographic area.)

“Relatively few people are alive now who witnessed epidemics of those diseases and their effects,” says Stanley Plotkin, the scientist who developed the rubella vaccine used in today’s MMR.

“As somebody who practiced university pediatrics in the 1950s and 60s, I don’t take those diseases lightly at all.”