Measles Vaccine (1963): John Enders and a Childhood Killer

The measles vaccine was first licensed in the United States on 21 March 1963, giving doctors a way to prevent one of the most contagious and deadly childhood diseases. It was the result of work begun in 1954 by the virologist John F. Enders and the physician Thomas C. Peebles at Boston Children’s Hospital, who were the first to grow the measles virus in the laboratory. Vaccination has since prevented tens of millions of deaths worldwide.

A universal childhood disease

Before the vaccine, almost every child caught measles. The virus spreads through the air and is so contagious that one case can infect 12 to 18 susceptible people. Most children recovered after a week or two of fever and rash, but measles can cause pneumonia, brain inflammation (encephalitis) and death, and it weakens the immune system for months afterwards.

In the United States in the decade before 1963, an estimated 3 to 4 million people were infected each year. Around 48,000 were admitted to hospital, about 1,000 developed encephalitis and roughly 400 to 500 deaths were reported annually. In poorer countries, where malnutrition made the disease far more dangerous, the toll was much higher.

Isolating the virus

Enders had already shared the 1954 Nobel Prize in Physiology or Medicine with Thomas Weller and Frederick Robbins for growing poliovirus in tissue culture, a technique that made the Salk polio vaccine possible. He turned the same method on measles.

In early 1954 Peebles went to the Fay School in Southborough, Massachusetts, where measles was spreading among pupils. He took blood samples from sick boys, and in one of them, from 13-year-old David Edmonston, the team succeeded in growing the virus in cultures of human kidney cells. Their results were published in 1954. The isolated virus became known as the Edmonston strain.

From laboratory to vaccine

The next step was to weaken, or attenuate, the virus so that it would trigger immunity without causing serious illness. The Boston group passed the virus repeatedly through human kidney cells, human amnion cells, fertilised chicken eggs and finally cultures of chick embryo cells. With each passage it adapted to its new hosts and became less harmful to people. Samuel L. Katz, a young paediatrician in Enders’ laboratory, led much of this work and the first trials in children around 1958 to 1960.

The trials showed that the weakened virus, called Edmonston B, protected children against measles. Its weakness was side effects: many children developed fever and some a mild rash, so it was often given together with a dose of immune globulin (antibodies) to soften the reaction.

On 21 March 1963 the US authorities licensed the first measles vaccines. Merck’s live Edmonston B vaccine was sold as Rubeovax. An inactivated (killed-virus) vaccine was licensed the same year, but it gave only short-lived protection and could cause a severe “atypical measles” in children later exposed to the virus, so it was withdrawn in the late 1960s.

Improvements and the MMR vaccine

At Merck, Maurice Hilleman and his team weakened the Edmonston virus further. Their “Moraten” (more attenuated Enders) strain, introduced in 1968, caused far fewer side effects and replaced the original vaccine in the United States. In 1971 Merck combined it with mumps and rubella vaccines to create the MMR vaccine, which allowed children to be protected against three diseases with one injection. A second dose was later recommended because a single dose leaves a small share of children unprotected.

Impact

The effect was dramatic. Reported US measles cases fell from several hundred thousand a year in the early 1960s to a few thousand by the 1980s. In 2000 the United States declared measles eliminated, meaning it no longer spread continuously within the country, although imported cases continued to cause outbreaks.

Worldwide, measles is estimated to have killed about 2.6 million people a year before vaccination became widespread in the 1980s. The World Health Organization estimates that measles vaccination prevented more than 50 million deaths between 2000 and the early 2020s alone. Measles has not been eradicated like smallpox, however, because very high vaccination coverage, around 95 per cent with two doses, is needed to stop it spreading, and outbreaks return where coverage falls.

Timeline

• 1954, early: Thomas Peebles collects blood samples during an outbreak at the Fay School in Massachusetts.
• 1954: Enders and Peebles report growing the measles virus in tissue culture; the Edmonston strain is isolated.
• 1958-1960: Trials of the attenuated Edmonston B vaccine in children are carried out.
• 1963, 21 March: The first live and inactivated measles vaccines are licensed in the United States.
• 1968: Hilleman’s further attenuated Moraten strain replaces Edmonston B.
• 1971: The combined MMR vaccine is licensed.
• 2000: Measles is declared eliminated from the United States.

Why it matters

The measles vaccine turned a disease that touched nearly every family into a preventable one. Building on the tissue-culture methods that also defeated polio, and on the tradition begun by Edward Jenner, it became one of the most effective tools in public health and remains a core part of childhood immunisation programmes around the world.