The Most Infectious Diseases in Human History and the Vaccines That Saved Us

Smallpox, polio and measles ravaged mankind, but vaccines we developed stopped them in their tracks.
Marcia Wendorf

Many people alive today have had no experience with infectious disease epidemics until the appearance of COVID-19 in the Spring of 2020. With COVID vaccines just beginning to be rolled out, we're going to take a look at three of the most infectious diseases in human history, and the vaccines that were developed to fight them.


Smallpox is caused by either of two virus variants — Variola major and Variola minor. The earliest evidence of smallpox is found in medical writings from 1500 BCE in India, and later, around 1122 BCE in China. The mummy of Egyptian Pharaoh Ramses V, who died around 1145 BCE, shows signs of smallpox.

Bangladeshi child with smallpox
Bangladeshi child with smallpox Source: James Hicks/Wikimedia Commons

European rulers who died of smallpox include Queen Mary II of England in 1694, Emperor Joseph I of Austria in 1711, Tsar Peter II of Russia in 1730, and King Louis XV of France in 1794. Smallpox survivors include the composers Mozart and Beethoven, Queen Elizabeth I of England, Frankenstein author Mary Shelley, and U.S. presidents George Washington and Abraham Lincoln.


From 735 to 737 CE, a smallpox epidemic in Japan killed up to one-third of the country's population. During the Middle Ages in Europe, travel for the Crusades caused smallpox to spread widely, and European explorers brought the disease with them to the New World. There, it decimated native populations who had no natural immunity to it. In Europe during the 18th century, smallpox killed an estimated 400,000 people each year.

Smallpox begins with a fever and vomiting, then small reddish spots called enanthem appear on the mucous membranes of the mouth and throat. Once these lesions rupture, they release large quantities of the virus into the body, which becomes covered with fluid-filled blisters called macules. The macules even extend to the palms of the hands and the soles of the feet. After a week, if the sufferer hasn't died, the macules scab over and fall off, however, they leave behind large scars and possibly cause blindness.

Illinois man in 1912 with smallpox
Illinois man in 1912 with smallpox Source: Illinois Dept. of Public Health/Wikimedia Commons

Smallpox is transmitted through the inhalation of airborne virus particles, but it can also be spread through contact with bodily fluids or contaminated objects such as bedding or clothing. Smallpox's death rate is around 30%, this rate is higher in infants. The last naturally occurring case of smallpox was in October 1977, and in 1980, the World Health Organization (WHO) considered the disease eradicated.

During the 9th century CE, the Persian physician, Rhazes, was the first to distinguish smallpox from measles and chickenpox. In 1700, English naturalist and physician Martin Lister received reports of smallpox inoculation from an employee of the East India Company who was living in China. That employee described smallpox scabs being powdered, then being blown up into the noses of healthy people who would go on to develop only a mild case of the disease, and would thereafter be immune.

In 1721, Lady Mary Wortley Montagu, who was the wife of the English ambassador to the Ottoman Empire, brought this method back to Britain after having observed it while living in Constantinople, modern-day Istanbul. However, it is the English physician Edward Jenner who is generally credited with creating the smallpox vaccine.

Jenner had noticed that milkmaids who contracted cowpox from the cows they milked were immune to smallpox. On May 14, 1796, Jenner scraped pus from cowpox blisters on the hands of a milkmaid, and inoculated an eight-year-old boy named James Phipps who was the son of his gardener. Jenner next exposed Phipps to smallpox to which the boy proved immune. By 1840, the British government was providing free cowpox vaccinations to its population.

Jenner called the material he used for the inoculation vaccine, from the Latin word vacca which means "cow". Napoleon, who at the time was at war with Britain, was so impressed by Jenner's vaccine that he had all of his troops vaccinated, and he awarded Jenner a medal, calling him "one of the greatest benefactors of mankind."

In 1802, Jenner was elected an honorary member of the American Academy of Arts and Sciences, and in 1806, he was elected a member of the Royal Swedish Academy of Sciences. Jenner died in 1823. In 1972, the U.S. stopped administering smallpox vaccinations, however, U.S. military personnel continued to be vaccinated up until 1990.

If you were born before 1972, chances are good that you have a smallpox vaccination scar on your upper left arm made by a bifurcated needle that had been dipped into the vaccine then used to puncture the skin of your arm several times.

Smallpox vaccine bifurcated needle
Smallpox vaccine bifurcated needle Source: CDC/Wikimedia Commons

In July 2018, the Food and Drug Administration (FDA) approved tecovirimat, the first drug approved for smallpox treatment. Antiviral drugs, such as cidofovir, have been shown to be useful in treating smallpox. Immunity to smallpox diminishes over time, but the smallpox vaccine is not routinely available to the U.S. public. The U.S. does however keep a stockpile of the vaccine in its Strategic National Stockpile.


During the early decades of the 20th century, poliomyelitis, or polio, haunted the Summers and Falls of the world's children. In tropical regions, it posed a threat year-round. Polio is spread by infected fecal matter that enters the mouth, or by food or water exposed to human feces or saliva. This made the virus especially prevalent in swimming pools and water holes where children had "accidents", and people swam with their mouths open.

Unlike many other communicable diseases, polio occurs naturally only in humans. While some cases of polio are mild or even asymptomatic, in 1% of cases, the virus enters the central nervous system (CNS) where it affects the spinal cord, the brain stem, or the brain's motor cortex. It can then cause paralysis.

Iron lungs
Iron lungs Source: Open source

This paralysis can occur in the legs or it can affect the entire body, including the breathing muscles of the diaphragm. In that case, sufferers must be placed in a negative-pressure ventilator known as an iron lung. Some polio patients remained in an iron lung for weeks, some for months, and some for their entire lives.

In 1921, 39-year-old Franklin Delano Roosevelt had just failed to be elected as Vice President in the 1920 presidential election when he contracted polio. The disease permanently paralyzed Roosevelt's legs, and he recuperated at a polio rehabilitation center that he founded in Warm Springs, Georgia.

FDR in wheelchair
FDR in wheelchair Source: Margaret Suckley/Wikimedia Commons

Overcoming his handicap, in 1929, Roosevelt became governor of New York state, and in 1932, he defeated the incumbent president, Herbert Hoover, to become the 32nd president of the United States. Taking office during the height of the Depression, Roosevelt created the New Deal, the Securities and Exchange Commission, the National Labor Relations Act, the Federal Deposit Insurance Corporation, Social Security, and the Fair Labor Standards Act of 1938.

In a time before the 22nd amendment to the U.S. Constitution, which limits presidents to just two terms, Roosevelt was reelected in 1936, 1940, and in 1944. During his third and a small part of his fourth terms, Roosevelt guided the U.S. through the dark days of World War II. While at Warm Springs on April 12, 1945, Roosevelt died. Just a month later, on May 8, 1945, the U.S. celebrated VE Day.

Other well-known people who have contracted polio are actress Mia Farrow, who was hospitalized for eight months, actor Donald Sutherland who developed a love for reading while bedridden, director Francis Ford Coppola who was confined to bed for over a year, and dancer Gwen Verdon who started dancing to strengthen her polio-affected legs.

Confined to his house by polio, Franklin Mars helped his mother make candy in their kitchen, and he went on to found the Mars Candy Company, maker of delights such as M&Ms, Snickers, Mars Bar, 3 Musketeers, Dove, Skittles, and Twix. Margarete Steiff, the founder of the Steiff Company which created the first teddy bears, was confined to a wheelchair because of polio. Famed science fiction author Arthur C. Clarke caught polio in 1962 and was confined to bed for months. Before his death in 2008, Clarke spent his final years in a wheelchair due to post-polio syndrome where symptoms return after years of being dormant.

In 1950, the first polio vaccine was developed by the Polish-American virologist Hilary Koprowski, and it used live but weakened virus. On April 12, 1955, University of Pittsburgh physician and medical researcher Jonas Salk introduced the first inactivated poliovirus vaccine. Administered by injection, the vaccine proved to be 99% effective.

In 1954, Polish-American physician and microbiologist Albert Sabin created an oral polio vaccine, and between 1956 and 1960, Sabin worked with Russian scientists to perfect the vaccine which was given en masse to Russian citizens. It wasn't until 1961 that Sabin's vaccine was widely available to Americans, and it went down especially smoothly since the vaccine was dripped onto a sugar cube.


During the 1950s, one of the most contagious diseases in the world, measles, raged through U.S. classrooms. Measles is so contagious that nine out of every ten people exposed to it will go on to develop the disease. Measles is not known to infect other animals.

Child with measles
A child with measles Source: CDC/Wikimedia Commons

The measles virus causes very high fevers of 104 degrees F (40 degrees C), inflammation of the eyes, spots known as Koplik's spots inside of the mouth, and a full-body rash. Measles is so insidious because it ushers in secondary infections such as ear infections, pneumonia, and encephalitis, which is an inflammation of the lining of the brain. Encephalitis can lead to seizures and blindness.

In 1529, a measles outbreak in Cuba killed two-thirds of that country's population, and in 1531, measles killed half the population of Honduras before going on to ravage Mexico and Central America. During the 1850s, measles killed 20% of Hawaii's population, and in 1875, it killed over 40,000 Fijians, which was one-third of that country's population. Between 1855 and 2005, it is estimated that measles has killed around 200 million people worldwide.

Aztec drawing of a measles sufferer
Aztec drawing of a measles sufferer Source: Wikimedia Commons

Before 1963, nearly every child in the U.S. had measles by the time they were 15-years-old. That year, American virologist John Enders and Dr. Thomas Peebles isolated the measles virus from blood samples taken from sufferers during an outbreak of the disease in Boston, Massachusetts. They went on to create the first measles vaccine.

In 1968, American microbiologist Maurice Hilleman improved upon that vaccine, and since 1968, the Edmonston-Enders vaccine has been the only measles vaccine given in the U.S. The measles vaccine is usually combined with vaccines for mumps and rubella, or German measles, and it is called the MMR vaccine.

Measles affects around 20 million people a year, mostly in developing areas such as Africa and Asia. In 1980, 2.6 million people died from measles, in 1990, that number was down to 454,000 and by 2014 global vaccination had brought that number down to 73,000. Then, in 1996, a former British doctor named Andrew Wakefield was contacted by a lawyer named Richard Barr who was looking for an expert witness for a class action lawsuit he was planning that alleged "vaccine damage" to children.

Wakefield and several colleagues signed on, and in 1998, Wakefield and 11 coauthors published a paper in the British medical journal The Lancet alleging a link between the MMR vaccine and autism. There was an immediate sharp drop in vaccinations which led to increased cases of measles and mumps. Studies undertaken by the U.S. Centers for Disease Control and Prevention (CDC) the American Academy of Pediatrics, and the UK National Health Service, were unable to find any link between the MMR vaccine and autism.

An investigation found that Wakefield had manipulated data and evidence, and had clear conflicts of interest. In 2004 Wakefield's article was removed from The Lancet, and in 2010, the journal completely retracted the article. That same month Wakefield was found guilty by the UK's General Medical Council, and he was struck off the Medical Register, meaning that he could no longer practice medicine in the UK.

Today, estimates are that just 70% of children receive the two recommended doses of the measles vaccine, and measles cases are now at a 20-year high, with deaths increasing 50% over the last four years.

It's easy to forget that COVID-19 is just one in a long line of diseases that have menaced mankind, and we have to thank an equally long line of scientists who have created the vaccines that have kept these diseases in check.

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