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26 January 2021

The Evolution of Vaccines: From Edward Jenner to Katalin Karikó

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It has been 225 years since the Englishman Edward Jenner (17 May 1749 – 26 January 1823) administered what is considered to be the first vaccine in history, but an intuitive grasp of this form of protection goes back many centuries. Since Jenner’s experiment, progress has been spectacular, culminating in the development of vaccines against COVID-19 within a matter of months. However, one of the most life-saving scientific breakthroughs also generates suspicions, a phenomenon as old as the first vaccine.

The earliest reference to the idea of immunity is attributed to the Greek historian Thucydides in 430 BC. During a plague that ravaged Athens, those who had survived the disease itself were entrusted with the care of the sick, as they would not suffer from it again. In the 10th century, Chinese doctors experimented with taking material from the pustules of smallpox sufferers to immunise others. Inoculation or variolation, the subcutaneous injection of powder from the scabs of the sick, was practised for centuries in China, India and Africa before reaching the attention of the Royal Society in the early 18th century, but without generating much interest. 

In 1716, the English writer and aristocrat Lady Mary Wortley Montagu learned of variolation during a stay in Turkey. She had her children inoculated and introduced the practice in England, where it did not initially take off, partly because 2-3% of those inoculated became ill rather than just being immunised. Variolation gained wider acceptance from 1721 onwards, when the Princess of Wales had her daughters inoculated, in view of the previous success of experiments on prisoners and orphaned children. Also instrumental was the contribution of the variolation campaign undertaken in Boston by the Reverend Cotton Mather and the physician Zabdiel Boylston.

Interactive timeline: History of vaccines

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The father of vaccines

In 1757, an eight-year-old boy, Edward Jenner, received his inoculation, like many others. But the man remembered today as the father of vaccines was not the first to modify the procedure towards what came to be called vaccination. The idea that people infected with the bovine version of smallpox (called cowpox) were immunised against the human disease had existed among Indian herders since ancient times, and had been known in England since at least the mid-18th century. In 1774, farmer Benjamin Jesty, who had suffered from cowpox, decided to infect his family with material from sick cows, confirming that this intervention protected against human smallpox. Finally, on 14 May 1796, Jenner vaccinated his first patient, 8-year-old James Phipps, using material collected from the milkmaid Sarah Nelmes. The boy, who was the son of Jenner’s gardener, did not fall ill when he was later exposed to smallpox. 

BBVA-OpenMind-Yanes-evolución vacunas de Edward Jenner a Katalin Karikó-2-Edward Jenner vacunando a su hijo. Crédito: Wellcome Library
Edward Jenner vaccinating his young child. Credit: Wellcome Library

Vaccination thus offered a safer method than variolation, but it was Jesty, not Jenner, who first applied it. Jenner’s essential contribution was to prove that vaccinated people were immune to subsequent variolation, as well as implementing the arm-to-arm method, using material from the pustules of one vaccinated person to immunise others. Thanks to Jenner’s work, vaccination spread around the world, although applying it to other diseases required a new breakthrough, since in the case of smallpox, cowpox conveniently provided an attenuated pathogen, something that did not exist for other infections. 

It was Louis Pasteur, Albert Calmette and Camille Guérin who, during the late 19th and early 20th century, found ways to attenuate pathogens by treating them with physico-chemical methods or by successive passages in cell culture. In 1955, one of the greatest milestones in the history of vaccines was achieved through a “collective effort that was put into defeating the most feared disease of the twentieth century,” University of Pittsburgh professor Carl Kurlander, producer of the award-winning documentary The Shot Felt ‘Round the World about Jonas Salk and his polio vaccine, tells OpenMind. Vaccines consisting of dead bacteria had already been developed in the 19th century; the polio vaccine was the second —after influenza— to be created using an inactivated virus that eliminated the risk from attenuated pathogens.

The biggest breakthrough in the last decade

Attenuation and inactivation are still used today, but the development of genetic engineering in the 1970s and 1980s paved the way for a new generation of synthetic vaccines, from those using proteins or other components to those that employ recombinant vectors, in many cases harmless viruses that act as vehicles into which parts of the target pathogen are introduced.

The latest technological breakthrough began to take shape in the 1990s thanks to the work of a number of researchers, including Hungarian biochemist Katalin Karikó and American immunologist Drew Weissman. The approach involves introducing the instructions, in the form of messenger RNA (mRNA), into the organism so that the body itself makes its own vaccine, the antigen that stimulates the immune response. While new vaccine platforms can be adapted to emerging viruses, mRNA vaccines are so tractable and versatile that they enable a vaccine to be created in just weeks, as demonstrated by the companies Moderna and BioNTech-Pfizer against COVID-19. As University of Virginia infectious disease specialist William Petri tells OpenMind, “mRNA vaccines are the biggest breakthrough in the last decade and a huge part of the future of vaccines.”

Las plataformas de ARNm son tan manejables y versátiles que permiten crear una vacuna en apenas semanas. Crédito: U.S. Secretary of Defense
mRNA vaccines are so tractable and versatile that they enable a vaccine to be created in just weeks. Credit: U.S. Secretary of Defense

But it’s not just vaccine technology that has progressed; so too have the processes for ensuring their safety and efficacy. Back in the time of Jenner, whose experiment would be considered unacceptable today, a significant proportion of the people vaccinated died. This was one of the reasons behind the early anti-vaccine movement, but not the only one; the enrichment of doctors and compulsory vaccination as a form of government control, especially of the poorer classes, were also criticised. Satirical cartoons of the time showed vaccinated people growing cow body parts, and anti-vaccine commentary proliferated in the form of letters to the editor in newspapers.

These days it is social media that spreads this persistent anti-vaccine sentiment, despite enormous advances since Jenner’s time. Today, “it is possible to develop vaccines quickly in the context of outbreaks; however, vaccine development already builds on existing science, as we have seen with COVID-19, and it is a reason why we shouldn’t see the vaccines as being ‘rushed’,” health sociologist Samantha Vanderslott of Oxford University’s Vaccine Group tells OpenMind

Communication, transparency and competent management will be essential to promote trust in vaccines at a particularly sensitive historical moment, because acceptance of vaccines is still fragile, Vanderslott notes. In short, as University of Pittsburgh professor emeritus of pharmacy Randy Juhl, co-author of the documentary on Salk and the polio vaccine, tells OpenMind, “history suggests that science, no matter how great, is only the beginning of implementation in a divided population.”

Javier Yanes


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