A history of vaccines
A HISTORY OF VACCINES
There was a one-in-three chance that a child born in the 15th century would die before the age of 15 – from, for example, pneumonia, whooping cough, dysentery, smallpox or flu. Even in the First World War, there was a bigger chance for soldiers to die from influenza than fighting. Vaccines have stopped many infections that kill eg. smallpox. Today, according to the World Health Organization, they help prevent as many as three million deaths a year. But we need to do a lot more to find good vaccines for diseases that affect the poorest people in the world most, for example malaria, tuberculosis and HIV. Swagata Yadavar follows the history of vaccination.
French biochemist Louise Pasteur in his laboratory. He developed the first vaccines against the chicken cholera and rabies with weakened bacteria. GL Archive/Alamy
There was smallpox in Egypt around the third century BCE. This was very dangerous and killed about a third of the people who caught it. A thousand years ago, in China and India, they had a simple form of vaccination. This was ‘variolation’ - they ground up smallpox scabs and blew this into the skin or the nostril of a healthy person. These people got a weak form of the disease but they were not so likely to die from it. This practice spread across Africa and the Middle East and reached Europe in the 18th century.
English physician and scientist Edward Jenner created the world’s first smallpox vaccine in 1796. Variolation was still often practised at that time, but there was a risk that the infected person could then spread the disease. In 1768, another English physician, John Fester, saw that people who got cowpox (similar to smallpox but much weaker) were immune to smallpox. Jenner gave the vaccine to the eight-year-old son of his gardener, James Phipps. He used pus from cowpox blisters on the hands of a milkmaid, Sarah Nelmes. Phipps had fever but didn’t have full smallpox. Later, when the boy had a vaccine of smallpox particles, he had no sign of infection. Jenner tested this on 23 more people. Soon, vaccination spread through Europe; Napoleon got the vaccine for all French soldiers. By 1840, Britain had banned variolation and gave free smallpox vaccination instead.
Louis Pasteur, a French biochemist, produced the first vaccine developed in a lab. It was for chicken cholera and he used weakened bacteria. This happened by accident. Pasteur had asked his assistant to inject chickens with active cholera bacteria. The assistant forgot and a month later injected the chicken with a month-old bacteria culture instead. The chicken became a little sick but didn’t die. Later when the same birds were injected with bacteria that killed other chickens, they survived. This proved that a vaccine of weakened organisms could give immunity.
Louis Pasteur also produced the first rabies vaccines. He grew the rabies virus in rabbits and weakened it by drying the nerves. He first tried out the vaccine on nine-year-old Joseph Meister, who had been bitten by a dog with rabies. The boy had 13 vaccines of the weakened rabies virus in 11 days, and never got rabies. This proved it was effective.
Cholera causes very bad diarrhoea, dehydration and, in serious cases, death. In 1892, Waldemar Haffkine, born in Ukraine, developed an effective vaccine against cholera with few side-effects. He was one of the first people to trial vaccines. Between 1893 and 1896, he vaccinated more than 40,000 people in India. Then all other scientists followed this method.
In 1896, German scientists Richard Pfeiffer and Wilhelm Kolle showed that vaccination with dead typhoid bacteria gave people immunity to typhoid. A year later, British scientist Almorth E Wright published a paper saying the same thing. Scientists agree that both Wright and Pfeiffer discovered the typhoid vaccine. Britain vaccinated all its soldiers during the First World War, and this stopped about 129,000 deaths.
In 1896, Bombay (now Mumbai) in India had a lot of bubonic plague and they asked Haffkine to help. He started to develop a vaccine in a small laboratory in a medical college. In three months, his vaccine was ready for human trials and in January 1897, Haffkine tried it on himself. Then he did a trial on people in a local prison. Haffkine’s vaccine had side-effects and did not give complete protection, but it halved the risk of dying.
French scientists Albert Calmette and Camille Guérin did their first human trial of a tuberculosis vaccine on babies at a hospital in Paris. The two scientists had been working to create a good weakened vaccine since 1900. They found that growing tuberculosis bacilli on bile from cows weakened the virus. Their vaccine was called Bacillus Calmette-Guérin or BCG.
Diphtheria was one of the most common infectious diseases and a very big cause of child deaths. Mortality rates were 40 per cent in Europe and the US. In 1926, Alexander Thomas Glenny improved diphtheria toxoid, an inactivated toxin, by treating it with aluminium salts. In the 1940s, scientists mixed this with tetanus toxoid and pertussis antigen to create the DTP vaccine (diphtheria-tetanus-pertussis).
Influenza killed 1 in every 67 US soldiers during the 1918-19 pandemic. So it was very important for the US army to develop a vaccine. With support of the army, researchers Thomas Francis and Jonas Salk developed the first inactivated influenza vaccine. This got approval for military use in the US in 1945 and for public use in 1946.
Jonas Salk (a US scientist) developed the first effective vaccine using an inactivated polio virus. They tested the vaccine on American school children from 1954. And US polio cases fell to just 161 by 1961. Albert Sabin (US scientist) developed an oral polio vaccine (OPV), containing live weakened virus in 1961. This became the standard polio vaccine.
The World Health Assembly decided smallpox must stop. In the next seven years, they improved the quality and safety of the vaccine. The programme had two goals: to vaccinate at least 80 per cent of the world population and to check and record cases well.
A child is vaccinated against tuberculosis in 1970s Sierra Leone, West Africa. During this period, the WHO launched the Expanded Programme of Immunization to protect against six serious diseases. Science History Images/Alamy
US scientists John Enders and Thomas Peebles collected blood from people with measles to isolate the virus and create a vaccine. Nine years later, they proved the safety and effectiveness of the measles vaccine. Now it usually comes with mumps and rubella vaccines as MMR (measles-mumps-rubella). (See also 1998 below.)
After the success of stopping smallpox, the World Health Organization started the Expanded Programme on Immunization (EPI) to make sure all children in the world got vaccines. The EPI recommended vaccines to protect against six diseases: tuberculosis (BCG), diphtheria, tetanus, pertussis (DTP), measles and polio.
There are almost 90 types of pneumococcal bacteria. Most cause pneumonia but some also cause blood infections. In 1977, pharmaceutical company Merck got the first licence for a pneumococcal vaccine against 14 types of the bacteria. This later increased to 23 types.
The World Health Assembly said the world was free of smallpox, two years after the last recorded case in Somalia.
US scientist Maurice Hilleman developed the first vaccine for hepatitis B by taking antigen (a protein the immune system produces) from gay men and intravenous drug users who had many cases of hepatitis. He developed a three-step process to purify the blood so that only the hepatitis B protein remained. The vaccine was approved in 1981 but, because people were worried about HIV infection, it was replaced by another that didn’t use human blood.
The World Health Organization, UNICEF, Rotary Foundation and others agreed to end polio by 2000 with the Global Polio Eradication Initiative. But this has still not yet happened. In 2020, there were 140 cases of wild polio and 1,039 cases that came from the vaccine. The problems are: war, lack of health infrastructure and communities being afraid the vaccine with harm them. There is still a lot of polio in Pakistan and Afghanistan. More people were against the vaccine when they found out that people gave fake hepatitis vaccinations to people to confirm the identity of Osama Bin Laden’s identity before the CIA killed him and others in Pakistan in 2011. Some vaccinating teams in Pakistan have been attacked and killed since them, especially in the northern tribal region.
A vaccine for rotavirus (the most common cause of diarrhoea in children) developed by Wyeth got a license in the US. But then they cancelled this because of risk of bowel obstruction. Eight years later, 2 companies, GlaxoSmithKline and Merck introduced new oral vaccines that were safe and effective in children.
British physician Andrew Wakefield published a paper in The Lancet linking the MMR vaccine with colitis and autism. None of the following studies found any evidence for this, but many people stopped agreeing to the vaccine. The Lancet cancelled the paper in 2010 after proving that Wakefield changed the data and had a conflict of interest in publishing the paper. Even today, anti-vaxxers still talk about the paper.
A Texan 14-year-old gets her HPV vaccine for primary prevention of cervical cancer. Jessica Rinaldi/Reuters/Alamy
Merck developed the first human papillomavirus (HPV) vaccine, Gardasil. It was approved in the US. Gardasil works against four types of HPV and helps prevent cervical cancer. In 2009, Cervarix by GlaxoSmithKline, which protects against two high-risk types of HPV, was approved.
Ebola is not common but the death rate from it is between 25 and 90 per cent. Between 2014 and 2016, around 11,000 people died of Ebola in West Africa. A vaccine, Ervebo, was developed in late 2019. This was effective against the Zaire Ebola virus and recommended for those over 18 years of age. In May 2020, a second vaccine given in two doses – Zabdeno-Mvabea – was approved to be sold in Europe by EMA - for children over one and adults.
Sources: Indian Journal of Medical Research; American Academy of Pediatrics; ‘The History of Vaccination’, Royal College of Physicians of Philadelphia.
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