The Invention of Tuberculosis Vaccine

The Invention of Tuberculosis Vaccine

As we all know tuberculosis has been killing millions of people for centuries. No country in this world is TB-free, and the disease is most prevalent in poor countries. It is a disease caused by Mycobacterium tuberculosis. For a human pathogen with no known environmental reservoir, Mycobacterium tuberculosis has honed the art of survival and has persisted in human communities from antiquity through modern times. 


While talking about transmission, the bacteria is transmitted in aerosols and the lungs are the prime site of disease symptoms, the main port of entry, and also the source of transmission. When infectious droplet nuclei containing aerosol are inhaled, the Microbacteia-laden droplet nuclei are formed. When the patient with active pulmonary TB coughs the viable bacilli can remain suspended in the air for several hours.   Infection can lead to primary TB disease with minor symptoms that are often overlooked before they recede. However, M. tuberculosis may persist in the host, causing latent TB infection (LTBI). About 90% of these individuals are thought to survive lifelong with LTBI; the remaining ca. 10% will develop active TB disease

In the year 1921, the Bacillus Calmette-Guerin (BCG) tuberculosis vaccine was administered for the first time in humans. French scientists Albert Calmette and Camille Guerin were the one developing the vaccine. 

The invention of the Tuberculosis Vaccine

While looking back to history, only in the 19th century, it was identified that the cause of Tuberculosis was Mycobacterium tuberculosis (M. tuberculosis) by German physician and microbiologist Robert Koch. After this there started different series of experiments and hypotheses.  Among many hypotheses, there was one, that the infection with the Mycobacterium bovis strain (found in cows) could offer protection against human tuberculosis. Unfortunately, it was stated that bovine tuberculosis was as harmful as the human strain. But finally, when Calmette decided to set foot in the search of a tuberculosis vaccine along with a junior researcher who later became a partner in 1908. They cultured a tuberculosis strain, which was isolated from a cow with tuberculous mastitis so that they could study it. They used to subculture the bacteria every three weeks. Subculturing is a process where some parts of the cultured bacteria are put into a new medium with the same composition. 

The process of inoculation started, the bacteria from the repeated subculture were then inoculated into young oxen. They initially observed that there was a sudden rise in the virulence of the bacteria. They did not stop there, they kept on producing subcultures, and after around 30 subcultures, the virulence started decreasing.  There is a saying when you have a vision and you believe in it, you will achieve it. After 13 years and 230 subcultures later, Calmette and Gurein finally were able to make totally harmless strain. They again tested it on oxen and they found that this strain did not make them sick but rather gave immunity to the tuberculosis. 

Now was the time for the real trial on humans. In the year 1921, Calmette decided that the time was ripened for the trial to happen in humans. He agreed to carry out this trial also because the infant’s life was in danger, as the mother had been suffering from tuberculosis. On 18th July 2921, Benjamin Weill-Halle and Raymond Turpin gave a dose of BCG by the oral route to the infant. Calmette believed that the gastrointestinal system was the most common natural route of tubercle bacillus infection. Weill-Halle then attempted the subcutaneous and cutaneous methods on other newborns, but the parents objected to the local reactions, therefore the oral technique was continued. Later The Pasteur Institute at Lille began to produce BCG vaccine for the mass population for use by the medical profession. 

Albert Calmette (without a lab coat) and Camille Guérin (on his right), with their team, at the end of the 1920s. They developed the vaccine against tuberculosis (BCG) in 1921.

Credit  : Institut Pasteur/Musée Pasteur

 The method of the BCG vaccine proved to be the safest. Slowly the statistics started to show a fall in tuberculosis mortality among the susceptible infants who had been vaccinated with BCG. Slowly the BCG vaccination was being taken outside of France. Spain and Scandinavian countries accepted it easily, but Britain and USA were still skeptical and sometimes even criticized.