COVID-19 has kept the world on the edge of its seat. Politicians, business people, working-class citizens and the marginalised – everyone is waiting with bated breath for the development of a vaccine for this pandemic. Vaccinations, since their administration, have possibly saved more lives than antibiotics.
The story of vaccines is one of gradual progress and laudable patience that stretches across the long history of medical science. A small peek into the professional lives of its pioneers gives us an idea of their tortuous journeys which ended in saving millions of lives.
From BC to AD
Jain philosophers in the sixth century B.C., referred to microscopic organisms existing in countless numbers, as Nigodas, but only in theory. Up to the 17th century, nobody could confirm their presence. No one knew why milk went sour or why meat smelled putrid after a few days.
An eyeglass maker from the Netherlands, Zacharias Janssen, was the first to invent the microscope in 1590. His invention played a crucial role in bringing microbes to light, both literally and figuratively. 80 years later, another Dutch scientist called Anton Van Leeuwenhoek, who took a keen interest in the art of magnification through lenses and microscopes, discovered molecular living beings in his tooth scrapings. He named the findings- Animalcules, which meant small animals.
Vaccination, as a procedure, is known to be in use in India and China since 1000 A.D. to develop immunity against smallpox. The disease caused rashes and pustules, and even death, due to fever and respiratory infection. Early vaccination (then known as variolation) required injecting a healthy person with scabs or pustules obtained from a patient. These foreign bodies excited the person’s immune system to produce antibodies, and thus, gave the person a fighting chance. However, immunisation was not guaranteed due to the pathogen’s high virulence.
In 1796, Edward Jenner discovered that vaccination with pustules from a milder form of the pox disease in cows gave permanent protection from the disease prevalent in humans. It was the world’s first live-vaccination.
Although Jenner received accolades for proving and improving a longstanding concept, Benjamin Jesty, in 1774, had already tried a similar experiment on his family. A cattle-breeder, he was well aware of the immunity to smallpox that the dairymaids carried due to their exposure to cowpox. During a local smallpox epidemic, he decided to vaccinate his family with cowpox. His sons remained immune to the disease even fifteen years post-vaccination.
Pasteur’s Entry and the Germ Theory
While Edward and Benjamin developed the vaccine, they were unaware of the causative agent behind smallpox. Soon, a French chemist, Louis Pasteur in the mid-1800s, presented the germ theory of diseases. He discovered that fermentation in alcohol happens due to the presence of rod-shaped microscopic organisms (hence the name bacteria, from the Greek bakteria, meaning staff or cane). He also realised that exposure to heat would kill such microorganisms, which is also the elementary principle behind pasteurisation.
At the time, fowl cholera was a notorious disease known to kill more than half the poultry during its outbreak. Pasteur managed to create a vaccine by attenuating (weakening) its germs. Interestingly, its development was a fortunate accident. Pasteur left for a brief vacation, leaving the cholera bacteria on the culture dishes. After resuming his work post-vacation, he realised that a few of the cultures had turned acidic. When he infected healthy chickens with germs from the acidic culture, they fell ill but didn’t die. Diminution of virulence by exposure to acid was a breakthrough.
Working with Emile Roux, a French bacteriologist, Pasteur also produced the first vaccine for rabies. But this time he was in a fix. Like in the case of Jenner, he was dealing with an organism nearly impossible to see under microscopes of his time. To achieve attenuation, Pasteur tried transmitting the disease to other animals. By hopping species, the virus mutated and became comparatively benign to humans. The process came to be known as in-vivo serial passage. From infected rabbits, Pasteur extracted its spinal cord, where he thought the virus was most concentrated. A finely ground concoction of the dried cord was then administered as a vaccine.
The anthrax vaccination also holds a special place among the legends of the vaccine. Both Pasteur and Henry Toussaint were in a neck-to-neck competition for its development. A German microbiologist, Robert Koch had already established that anthrax could survive indefinitely in the form of spores.
Toussaint, a French veterinarian, speculated that the pathogens are much more virulent in the blood of infected bovines. After its extraction, he heated the blood at 55o Celsius and then filtered it through a 12-layer filter to produce an attenuated vaccine. He also tried to weaken the bacteria by using phenol acid. Both experiments gave positive results. But to his disappointment, Pasteur was the first to exhibit an identical vaccine publicly and took most of the credit.
Joseph Lister, a British surgeon, was piqued by the findings of Pasteur and thus concluded that the germs were behind the infections. To test his theory, he instructed to keep the surgery wards spotless and wounds disinfected with antiseptics. The results were astonishing. The post-op survival rate increased from 50 to 85 per cent. Consequently, sterilisation became an industry standard.
Another progress came with the development of the inactivated vaccines. In 1886, Daniel Elmer Salmon and Theobald Smith presented their findings on immunisation of pigeons from hog cholera by using its pathogens killed by exposure to heat. The research by Salmon and Smith bore fruit during the development of plague vaccine in India.
The Bubonic plague of 1896 had India under its clutches with its epicentre in Bombay. The colonial government summoned Dr Waldemar Haffkine, a bacteriologist, to find its cure. Dr Haffkine decided to take up heat-inactivated vaccination. After extracting the pathogen from infected rats, he grew them in a meat broth (which acted like a petri dish) under the layer of homemade ghee or coconut oil. The bacteria, within weeks, cultured into thread-like structures, now commemoratively known as Haffkine Stalactites . These stalactites were then killed by heat and injected into a healthy human as a vaccine.
The BCG (bacilli Calmette-Guerin) vaccine is also distantly related to Pasteur. His protégé, Albert Calmette, started culturing a strain of bacteria obtained from a cow in 1906 with a veterinarian named Camille Guerin. In the beginning, they mistook the bovine tuberculosis strain for the human tuberculosis strain. They attenuated the pathogen by allowing it to evolve for 13 years in different lab-controlled conditions known as in-vitro serial passage. The final result was a mutated virus ready to be used as a vaccine.
History has showed us that the process of finding a vaccine is an arduous undertaking of trial and error. Now, with humanity battling a pandemic, scientists are working around the clock to find a vaccine for COVID-19. Here’s to hoping their names are added to this history soon.
 Chirico JoAnn, Global Problems-Global Solutions: Prospects for a Better World, (USA, Sage Publications, 2018), Pg C4. XXII.iv
 Wiley Kristi, A to Z of Jainism, (Toronto, The Scarecrow Press, 2009), Pg 156
 Beck Roger, World History: Patterns of Interactions, (Florida, Houghton Mifflin School, 2010), Pg 627
 Pelczar Michael J, Microbiology – An Application based Approach, (New Delhi, Tata McGraw Hill, 2010), Pg pr4
 Nijkamp Frans. P, Principles of Immunopharmacology, (Germany, Birkhauser Verlag, 2005), Pg 231
 Someswara N, Immortal Lights: Edward Jenner, (Banglore, Sapna Book House, 2005), Pg 32
 Plotkin Stanley, Vaccines, (China, Saunders, 2004), Pg 2
 Plotkin Stanley, Vaccines, (China, Saunders, 2004), Pg 2
 Plotkin Stanley, History of Vaccine Development, (New York, Springer, 2011), Pg 18
 Gaynes Robert P, Germ Theory: Medical Pioneers in Infectious Diseases, (USA, ASM, 2011) Pg 114
 Davidson Tish, Vaccines: History Science and Issues, (California, ABC-CLIO, 2017), Pg 31
 Plotkin Stanley, History of Vaccine Development, (New York, Springer, 2011), Pg 39
 Davidson Tish, Vaccines: History Science and Issues, (California, ABC-CLIO, 2017), Pg 32
 Beck Roger, World History: Patterns of Interactions, (Florida, Houghton Mifflin School, 2010), Pg 764
 Jhala H.I, W.M.W. Haffkine Bacteriologist A Great Saviour of Mankind, (Bombay, Haffkine Institute, 1967), Pg 111
Davies Peter, Clinical Tuberclosis, (New York, Hodder Arnold, 2013), Pg 411
(Edited by Sruthi Radhakrishnan)