A history of vaccines
Early records show smallpox was found in Egypt around the third century BCE. Among the deadliest diseases, smallpox killed about a third of the people it infected. Vaccination in a crude form existed in China and India a thousand years ago. A process known as ‘variolation’ involved grinding up smallpox scabs and blowing the material into the skin or the nostril of a healthy person. They would get a mild form of the disease but become less likely to die from it. This practice spread across Africa and the Middle East before reaching Europe in the 18th century.
English physician and scientist Edward Jenner created the world’s first smallpox vaccine in 1796. During his time, variolation was still commonly practised, with the risk that the infected person could then become a carrier. In 1768, another English physician, John Fester, had noted that those who were infected with cowpox, a disease similar to smallpox but much milder, were immune to smallpox. Jenner inoculated the eight-year-old son of his gardener, James Phipps, using pus from cowpox blisters on the hands of a milkmaid, Sarah Nelmes. Phipps showed symptoms of fever but no full-blown infection. Later, when the boy was injected with smallpox particles, he showed no sign of infection. Jenner tested his hypothesis on 23 more people. Soon, vaccination spread throughout Europe; Napoleon had all French soldiers inoculated. By 1840, Britain had banned variolation and introduced free smallpox vaccination instead.
Louis Pasteur, a French biochemist, produced a laboratory-developed vaccine (the world’s first) against chicken cholera by using attenuated or weakened bacteria. It happened by accident. Pasteur had asked his assistant to inject chickens with virulent cholera bacteria. The assistant forgot and a month later injected the chicken with a month-old bacteria culture instead. The chicken became mildly 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 developed from weakened organisms was effective in giving immunity.
Louis Pasteur also produced the first rabies vaccines. He grew the rabies virus in rabbits and weakened it by drying the affected nerve tissue. He first tried out the vaccine on nine-year-old Joseph Meister, who had been bitten by a rabid dog. The boy received 13 inoculations of the weakened rabies virus over 11 days, after which he never developed rabies, proving its efficacy.
Cholera causes severe diarrhoea, dehydration and, in serious cases, death. In 1892, Ukrainian-born Waldemar Haffkine developed an effective vaccine against cholera with few side-effects. He was among the first to conduct field trials. Between 1893 and 1896, he vaccinated more than 40,000 people in India. Haffkine’s methods of studying efficacy became the norm for vaccine trials.
In 1896, German scientists Richard Pfeiffer and Wilhelm Kolle demonstrated that vaccination with dead typhoid bacteria resulted in immunity against it. A year later, British scientist Almorth E Wright published a paper with a similar finding. Both Wright and Pfeiffer are credited for finding the typhoid vaccine. The impact of the vaccine was clear when Britain vaccinated all its troops during the First World War, preventing an estimated 129,000 deaths.
In 1896, the city of Bombay (now Mumbai) in India was struck by bubonic plague and Haffkine was asked to help. He started to develop a vaccine in a makeshift laboratory in a medical college. In three months, his vaccine was ready for human trials and in January 1897, Haffkine tried it on himself. Soon a trial followed on inmates of a local jail. Haffkine’s vaccine had side-effects and did not provide complete protection, but it halved the risk of dying.
French scientists Albert Calmette and Camille Guérin conducted their first human trial of a tuberculosis vaccine by injecting infants at a hospital in Paris. The two scientists had been working to create an effective attenuated or weakened vaccine since 1900. They found that growing tuberculosis bacilli on bovine bile led to a weakening of the virus. Their vaccine was called Bacillus Calmette-Guérin or BCG.
Diphtheria was one of the most common infectious diseases and a major cause of childhood deaths, with mortality rates as high as 40 per cent in Europe and the US. In 1926, Alexander Thomas Glenny increased the effectiveness of diphtheria toxoid, an inactivated toxin, by treating it with aluminium salts. In the 1940s, it was combined with tetanus toxoid and pertussis antigen to create diphtheria-tetanus-pertussis or the DTP vaccine.
With influenza causing death in 1 in every 67 US soldiers during the 1918-19 pandemic, the development of a vaccine was of prime importance to the US army. With its support, researchers Thomas Francis and Jonas Salk developed the first inactivated influenza vaccine, which was approved for military use in the US in 1945 and for public use in 1946.
The first effective vaccine using an inactivated polio virus was developed by US scientist Jonas Salk. The vaccine was tested in American school children from 1954. Thanks to a mass immunization campaign, US polio cases fell to just 161 by 1961. An oral polio vaccine (OPV), containing live weakened virus, was developed by US scientist Albert Sabin in 1961. This became the standard polio vaccine.
The World Health Assembly passed a resolution for the worldwide eradication of smallpox. In the next seven years, efforts were made to improve vaccine quality and safety. The programme had two goals: to vaccinate at least 80 per cent of the global population and to put surveillance and containment systems in place.
US scientists John Enders and Thomas Peebles collected blood samples from a measles outbreak to isolate the virus and create a vaccine. Nine years later, they succeeded in proving the safety and effectiveness of the measles vaccine, which is now usually clubbed with mumps and rubella vaccines as measles-mumps-rubella (MMR). (See also 1998 entry.)
After the success of the smallpox eradication programme, the World Health Organization launched the Expanded Programme on Immunization (EPI) to ensure all children across the world had access to vaccines. The EPI recommended vaccines to protect against six diseases: tuberculosis (BCG), diphtheria, tetanus, pertussis (DTP), measles and polio.
There are almost 90 strains of pneumococcal bacteria, with most causing pneumonia but some also leading to bloodstream infections. In 1977, pharmaceutical company Merck received the first licence for a pneumococcal vaccine against 14 strains of the bacteria, which was later expanded to 23 strains.
The World Health Assembly declared the world free of smallpox, two years after the last recorded case in Somalia.
US scientist Maurice Hilleman developed the first vaccine for hepatitis B by harvesting antigen, a protein produced by the immune system, from gay men and intravenous drug users who had a high incidence 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, due to concerns about HIV infection, it was replaced by another that didn’t use human serum.
The World Health Organization, UNICEF, Rotary Foundation and others passed the Global Polio Eradication Initiative, intending to rid the world of the disease by 2000. This has not yet been achieved. In 2020, there were 140 cases of wild polio and 1,039 cases of vaccine-derived cases in the world. Among the obstacles are war, lack of health infrastructure and opposition from communities fearing vaccination might cause harm. Polio is still endemic to Pakistan and Afghanistan. Opposition to vaccination grew when it was revealed that fake hepatitis vaccinations were conducted to ascertain Osama Bin Laden’s identity before his killing by the CIA and others in Pakistan in 2011. There have been deadly attacks on vaccinating teams in the country since, especially in the northern tribal region.
A vaccine for rotavirus (the most common cause of diarrhoeal disease in children) developed by Wyeth was licensed for use in the US, only to be withdrawn due to increased risk for bowel obstruction. Eight years later, rival manufacturers GlaxoSmithKline and Merck introduced new oral vaccines that were safe and effective in children.
In 1998, British physician Andrew Wakefield published a paper in The Lancet linking the MMR vaccine with colitis and autism. Even though none of the subsequent studies found any evidence to support a link, the controversy was enough to cause a drop in vaccination uptake. The Lancet retracted the paper in 2010 after an investigation showed Wakefield had manipulated data and had a conflict of interest in publishing the paper. Even today, the paper is still cited by anti-vaxxers.
The first human papillomavirus (HPV) vaccine, Gardasil, was developed by Merck and approved in the US. Gardasil works against four types of HPV and is a tool for the primary prevention of cervical cancer. In 2009, Cervarix by GlaxoSmithKline, which protects against two high-risk types of HPV, was approved.
Ebola occurs rarely but has death rates ranging 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 which was found to be effective against the Zaire Ebola virus and recommended for those over 18 years of age. In May 2020, a second vaccine administered in two doses – Zabdeno-Mvabea – was approved to be sold in Europe by EMA. The vaccine was approved for children over the age of one and for adults.
Sources: Indian Journal of Medical Research; American Academy of Pediatrics; ‘The History of Vaccination’, Royal College of Physicians of Philadelphia.