The race for a cure: how we found vaccines for 4 of history's most dangerous diseases

The word ‘vaccination’, from Jenner’s invented Latin name for cowpox, was coined in 1800 by Plymouth surgeon Richard Dunning. Eighty years later, in homage to Jenner, Louis Pasteur proposed that the word should cover all inoculations that protect against infections. Pasteur is best known for inventing the first vaccine against rabies, but he also developed vaccines against the bacterial infections cholera and anthrax.

Two other landmark vaccines were those against the dreaded tuberculosis and polio infections. The BCG vaccine against tuberculosis took more than 15 years to perfect. Its early success was marred in 1929 when 72 children died in Lübeck, Germany after being given BCG accidentally contaminated with live tuberculosis. Almost 30 years later, the first polio vaccination campaign in America was nearly derailed by a similar catastrophe, when batches of Jonas Salk’s vaccine were contaminated with live poliovirus that caused fatal outbreaks of paralytic polio.

• Listen | Gareth Williams explores previous efforts to combat lethal diseases, from smallpox to polio

Who were the first anti-vaxxers?

Why would anyone not want to be vaccinated against dangerous or even lethal infections? Opposition to Jenner’s vaccine sprang up almost immediately, with religious objections against this ‘bestial’ practice which defied the will of God to determine how and when everyone must die. Many doctors also railed against vaccination, blaming it for side-effects including blood-poisoning and syphilis (both genuine, but rare) and unsubstantiated or invented complications such as cancer, madness and – with graphic illustrations in medical journals – the transformation of vaccinated children into cows.

• The history of vaccination: from Edward Jenner to anti-vaxxers

This brings us back to the present day. Medical science has come a long way since Jenner, who knew nothing about immunity or even that infections were caused by ‘germs’. Today, the anti-vaccination movement is alive and well, and already opposed to Covid-19 vaccines. Last year, the World Health Organisation included the refusal to be vaccinated among the top 10 threats to global health. It will be interesting to see how well vaccines and anti-vaccinationists weather the Covid-19 pandemic.

In the meantime, spare a thought for the place where it all started. Dr Jenner’s House in Berkeley, Gloucestershire is where Jenner did his experiments with cowpox (and much else), wrote his most famous work and laid the foundations of vaccination and immunology. He died there and is buried in the church next door. The house should be a World Heritage Site, but like other small provincial museums with no government funding, may not survive the Covid pandemic. Please visit jennermuseum.com – and keep your fingers crossed that Dr Jenner’s House will still be there when, thanks to vaccination, the world gets back to normal.

Edward Jenner’s eureka moment for smallpox

Edward Jenner (1749–1823) was more than a jobbing doctor in rural Gloucestershire. He was schooled in the science of medicine by John Hunter, the ‘father of experimental surgery’, and was appointed a Fellow of the Royal Society after clarifying the nesting habits of the cuckoo. In 1796, he did experiments that proved that healthy children inoculated with cowpox couldn’t catch smallpox. We know now that both diseases are caused by viruses so similar that the immunity produced by the benign cowpox also protects against smallpox, which killed up to half of its victims.

According to legend, Jenner got the idea from a milkmaid who told him of the belief among farmers that anyone who caught cowpox (which caused characteristic blisters on cows’ teats) was forever safe from smallpox, and could even nurse patients dying of the disease. More likely, Jenner noticed that people who had caught cowpox failed to react to ‘variolation’, the deliberate infection of healthy subjects with a tiny dose of smallpox pus scratched into the skin in the hope of protecting them against a future attack of smallpox. Variolation certainly sounds bizarre, but it often worked and had a much lower mortality than natural smallpox.

In May 1796, Jenner removed fluid from a cowpox blister on the hand of a milkmaid named Sarah Nelmes, who had been infected by her cow, Blossom. He scratched the fluid into the arm of James Phipps, the eight-year-old son of his gardener, who developed a vaccination blister and a mild fever but quickly recovered. Some weeks later, Jenner variolated the boy – and made the “delightful” observation that the tell-tale pustules of artificial smallpox failed to appear. Jenner followed up this eureka moment with a dozen more cowpox inoculations and almost 30 reports of people with previous cowpox who had later been exposed to smallpox but didn’t catch it.

Jenner’s initial paper was rejected by the Royal Society, so he self-published An Inquiry into the Causes and Effects of the Variola Vaccinae, or Cowpox. The Inquiry came out in September 1798; it was an illustrated do-it-yourself guide to vaccination and soon became a bestseller.

Jenner’s admirers included Napoleon, who declared: “I can refuse this man nothing

Vaccination spread rapidly across Britain and into Europe and North America. From 1802–05, the extraordinary Royal Philanthropic Expedition organised by King Charles IV of Spain took Jenner’s invention literally around the world, via the Spanish colonies in the Caribbean, South America and the Indian Ocean.

To millions around the world, Jenner was a hero. His admirers included Napoleon Bonaparte (who declared “I can refuse this man nothing” – even though France was at war with England) and the tsar and empress of Russia (who sent him a diamond ring “from Marie”). In 1806, the American president Thomas Jefferson predicted that Jenner would be remembered as the man who rid the world of smallpox.

When was small pox eradicated?

By the time of Jenner’s death in 1823, vaccination had greatly reduced smallpox cases in Europe and America and completely cleared the infection from northern Italy. Jefferson’s prophecy ultimately came true in 1980, when the 11-year intensive global vaccination campaign mounted by the World Health Organisation finally achieved ‘Target Zero’ – the complete extermination of smallpox.

Jenner was handsomely rewarded during his lifetime by honoraria from parliament and, posthumously, by having his statue unveiled by Prince Albert in Trafalgar Square in 1858. By then, both Jenner and vaccination were under attack by the anti-vaccination movement. His enemies had their revenge in 1862, when Jenner’s statue was moved from its position of national prominence in Trafalgar Square to Kensington Gardens, where it can be seen today.

Louis Pasteur’s ingenuity takes a bite out of rabies

Louis Pasteur (1822–95) was a biologist who began his career studying an infection of silkworms that threatened to devastate the French silk industry. Later, he developed weakened (‘attenuated’) strains of cholera and anthrax bacteria; each caused mild symptoms in healthy animals but left them protected against the infection, which was usually fatal.

Pasteur took ‘attenuation’ to new levels of ingenuity while trying to weaken the infectious agent of rabies, which he managed to extract from the saliva of rabid dogs. We now know that rabies is caused by a virus that enters nerves exposed by a rabid dog’s bite, and tracks back up the nerves to the brain, where it produces a severe, almost universally fatal infection. Depending on the length of the nerve, the back-tracking can take many days, providing doctors with a life-saving window of opportunity to stimulate the patient’s immune system and wipe out the virus before it reaches the brain.

Pasteur attenuated rabies by injecting infected saliva extracts into the brain of a live rabbit, then removing the spinal cord after death and drying this for several days. Injected extracts of spinal cord reduced the patient’s risk of developing rabies – the first effective treatment for the disease.

Interestingly, the dog that bit Pasteur’s celebrated first case – nine-year-old Joseph Meister, brought from Alsace to be saved by Pasteur – may not have had rabies. Nonetheless, Meister’s miraculous survival helped to cement Pasteur’s reputation, and patients flooded to his lab in the Latin Quarter of Paris from across France, Germany and even Russia.

Being non-medical, Pasteur was never allowed to inject his vaccine into patients. However, like Jenner before him, the Frenchman became an international hero. The network of Pasteur Institutes established across the world has developed many successful vaccines.

Three French scientists turn Tuberculosis against itself

Tuberculosis (TB) – known as ‘consumption’ because the patient’s flesh seemed to melt away – was an even greater killer than smallpox. The infection destroys the lungs (coughing up blood is a common symptom) and can spread to the kidneys, bones and brain. Before the discovery of the powerful antibiotic streptomycin in 1943, the diagnosis of tuberculosis was often a death sentence, which the wealthy lived out in sanatoria high in the Alps where the clear mountain air was marketed (wrongly) as curative.

The causative bacterium, a rod-shaped bacillus with a tough coat, was discovered in 1882 by Robert Koch – instantly transforming him into a worldwide medical celebrity. Koch also invented a so-called cure which he named ‘tuberculin’ and tried out on his wife, Hedwig. She survived tuberculin treatment; unfortunately, so did Koch’s bacillus. Early attempts to produce a vaccine also failed.

What does BCG stand for?

Success eventually came to Albert Calmette (1863–1933) and Camille Guérin (1872–1961), working at the Pasteur Institute that Calmette set up in Lille. They began with the bovine type of TB, isolated from the milk of an infected cow and weakened by repeated ‘passages’ (transfers into a special culture medium, which they devised after years of trial and error – the winning recipe involved potatoes, glycerine and ox bile). The original bovine bacterium killed guinea pigs at tiny doses, but after 39 passages became harmless – yet able to protect animals against human tuberculosis.

The ‘Bacille Calmette-Guérin’ (BCG) vaccine was first tried on a baby in Paris in 1921. By 1928, 50,000 French children had been vaccinated, cutting their risk of dying after coming into contact with a TB patient from one in four to one in 50. BCG was highly effective when administered intradermally (into the skin) using a multi-pronged injection device. Its routine use was discontinued in Britain in 2005, but is still indicated in regions where TB remains prevalent, especially in association with Aids.

Two Americans battle to beat Polio

For a 40-year period beginning in 1916, polio was one of every parent’s worst nightmares: it could drop without warning into any home and paralyse or kill a child overnight. Paralysis might affect just one hand, or every muscle from the neck down – in which case artificial respiration (for example with the iron lung) was needed to keep the patient alive.

In 1953, polio was second only to the atomic bomb as the average American’s greatest fear

In America, the wealthy used to desert cities in advance of the polio season each summer; and in 1953, polio was second only to the atomic bomb as the average American’s greatest fear. The cause was known to be a small gut virus, but every treatment tried – including vitamin C, electric shocks and branding the back of a paralysed child with a red-hot poker – proved useless. Experimental vaccines were developed during the 1920s, but these either failed or proved dangerous.

Polio vaccine history

During the 1950s, two brilliant American scientists were locked in a ruthless race to perfect their own polio vaccines. Jonas Salk (1914–95) inactivated polioviruses using formalin (embalming fluid), and finally produced an injectable ‘dead’ polio vaccine that was tested in 1954 in more than 1.8 million American and Canadian schoolchildren. The outcome – “It works and is safe” – was announced to an international media frenzy in April 1955. Church bells were rung across America, and Salk became a cult figure.

Meanwhile, Albert Sabin (1906–93) was still working on his alternative vaccine. This used live polioviruses that he had attenuated in the lab, and was given orally. Sabin resented Salk’s success and repeatedly mocked him as a “kitchen chemist”. Neither man behaved well, leading one distinguished American historian to describe them as “a pair of real bastards”. Sabin’s oral polio vaccine was introduced in 1965, by which time Salk’s vaccine had almost eliminated polio from America.

Neither vaccine is perfect, but both can be highly effective. Sabin’s vaccine largely superseded Salk’s because it is cheaper and easier to administer, especially in large-scale vaccination programmes. Using both vaccines, the Global Polio Eradication Initiative has almost wiped out polio.

Gareth Williams is an emeritus professor of medicine at the University of Bristol. His books include Paralysed with Fear: The Story of Polio (Palgrave Macmillan, 2013) and Unravelling the Double Helix: The Lost Heroes of DNA (W&N, 2019)

This content first appeared in the January 2021 issue of BBC History Magazine