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In countries with a lot of tuberculosis, WHO notes, BCG is given to babies or small children, and it is one of the oldest vaccines still in use. The name stands for Bacille Calmette-Guerin: the bacillus of Calmette and Guerin. Behind those three letters is one of the slowest, most patient pieces of laboratory work in medical history. This post covers who the two scientists were, how they turned a dangerous germ into a vaccine, what went wrong along the way, and the numbers that make TB a pressing problem for India.
Who were Calmette and Guerin?
A historical overview by Line Bourel in the Journal of Clinical Practice and Research (2024) gives their backgrounds. Albert Calmette was born in Nice in 1863 and trained as a naval doctor. In 1891 he set up the Pasteur Institute in Saigon, the first outside France, and in 1894 he was sent to Lille to found a new Pasteur Institute there.
Camille Guerin was born in Poitiers in 1872. His father died of tuberculosis in 1882, when Camille was 10. He trained as a veterinary surgeon at Alfort and joined Calmette in Lille in 1897. Calmette was the organiser and public voice; Guerin was the meticulous hands at the bench.
How did they weaken the TB bacterium?
Their starting point was *Mycobacterium bovis*, the tuberculosis bacterium of cattle. According to the same review, from 1908 they grew it on slices of potato soaked in glycerinated beef bile, then moved a little of the growth to fresh medium, again and again. Each transfer is called a passage. Over many passages the strain lost its ability to cause disease while keeping enough of its surface features to train the immune system.
The work was interrupted when Lille was occupied during the First World War. In 1921, after 230 passages, they judged the strain ready, and the first human dose was given on 18 July 1921.
A genome study of BCG strains in PLOS ONE (2013) confirms the timeline: the strain "was attenuated after 230 passages over a period from 1908 to 1921". Comparing genomes, the authors found that some key deletions, including one called RD1, most likely happened during those first 13 years of passages.
Worked example: what does 230 passages in 13 years mean?
Days available: 13 years × 365 days = 4,745 days.
Days per passage: 4,745 / 230 = 20.6 days, so about one transfer every three weeks.
Weeks check: 13 × 52 = 676 weeks; 676 / 230 = 2.9 weeks.
That is a transfer roughly every three weeks for 13 years, including the wartime years when, the review notes, research had to be interrupted. Guerin, Bourel writes, kept the culture going with remarkable tenacity.
What went wrong after 1921?
Once BCG spread to other countries in the 1920s, each laboratory kept its own culture. The PLOS ONE study explains that these "daughter strains" were passaged separately from 1921 to 1966 and drifted apart genetically, which is why BCG today comes in several named strains such as Danish, Pasteur and Tokyo. In 1966, WHO recommended that vaccines be made from a frozen seed lot with no more than 12 further passages, to stop the drift.
There was also a tragedy. Bourel's review records that in 1930, 72 children in Lubeck, Germany, died after vaccination. The investigation found that a virulent TB strain had contaminated the vaccine during handling. BCG itself was cleared, but the disaster hurt Calmette deeply. He died in 1933. Guerin lived until 1961 and kept working to spread BCG vaccination worldwide.
Does BCG still matter?
Yes, especially in India. The WHO tuberculosis fact sheet says 10.7 million people fell ill with TB in 2024 and 1.23 million died, and that India had 25% of the world's new cases. That is about 0.25 × 10.7 million = 2.7 million people. WHO says BCG, given to babies or small children in certain countries, "prevents deaths from TB and protects children from serious forms of TB."
It is not a perfect vaccine. Bourel notes that in clinical trials its estimated efficacy has ranged from 80% protection to no benefit, for reasons still not fully understood. That is one reason researchers are still working on better TB vaccines.
Which ideas link to your syllabus?
Attenuated vaccines. The NCERT Class 12 chapter Human Health and Disease explains that a vaccine can be an "inactivated/weakened pathogen" that builds memory B and T cells. BCG is a live, weakened bacterium.
Pathogen versus strain. BCG is a weakened strain of *M. bovis*, the cattle TB bacterium, not of *M. tuberculosis* itself.
For the bigger story of how vaccines began, read our post on Edward Jenner and vaccination.
What can a student take from Calmette and Guerin's way of working?
Split the work by strength. One built institutions and argued the case; the other kept the experiment alive.
Respect slow methods. No single passage looked like progress. The result came from doing a dull step 230 times without breaking the chain.
Learn from failure honestly. Lubeck showed that a good vaccine can be ruined by poor handling, which is why seed lots and quality control matter.
If you find immunity topics blur together, the Fermi Concept Library covers every concept in biology, each with its own lesson and its place in the map, so you can see how vaccines, memory cells and antibodies connect.
Try it now: ask a family member to check your vaccination card for the BCG entry, and note the age at which it was given.
