Weakening a killer, one culture at a time
Starting in 1908 at the Pasteur Institute in Lille, the physician Albert Calmette and the veterinarian Camille Guerin set out to produce a strain of tuberculosis-related bacterium weak enough to be given safely to people yet still capable of training the immune system to recognise the disease. Their method was repetition: they grew a virulent strain of Mycobacterium bovis, related to the bacterium that causes human tuberculosis, on a bile-containing culture medium and subcultured it again and again, checking periodically whether it could still cause disease in test animals. This continued for thirteen years and 239 successive subcultures, through the disruption of the First World War, until by 1919 the strain, by then known as Bacille Calmette-Guerin, or BCG, had lost the ability to cause tuberculosis in the animals it was tested on.
The first vaccination, 1921
Calmette and Guerin moved to the Pasteur Institute in Paris in 1919, and in 1921 the attenuated strain was given to a newborn infant at the Hopital de la Charite, the first use of what would become BCG vaccination in humans. The approach relied on giving a live but weakened bacterium rather than a killed one or a purified fragment of it, on the reasoning, drawn partly from earlier work by the Norwegian researcher Kristian Feyer Andvord, that a living organism, even a weakened one, would provoke a more durable immune response than dead material. Early use expanded gradually through the 1920s as the vaccine’s apparent safety in the initial cases built confidence in the method.
A contamination that turned deadly
That confidence was badly shaken in 1930, when a vaccine batch administered in Lubeck, Germany turned out to have been contaminated with the original virulent tuberculosis strain, apparently through storage alongside it in the same incubator. Of 251 infants given the contaminated batch, 173 developed tuberculosis and 72 died, a disaster that became public knowledge and weighed heavily on Calmette, who died three years later. Production and safety practices were overhauled, and mass vaccination resumed in many countries by 1932, but the episode remains part of BCG’s history as a reminder that a live attenuated vaccine depends entirely on strict separation from the virulent organism it is derived from.
Protection that will not settle on one number
Once safety practices recovered, BCG’s protective effect turned out to be real but far from uniform. A 1994 review put its overall effect at roughly halving the risk of tuberculosis, but individual trials have found very different results depending on location: studies in the United Kingdom have consistently shown protection in the range of 60 to 80 percent, while trials conducted nearer the equator have sometimes found no measurable protective effect at all. How long protection lasts is similarly unsettled, with one long-running UK study finding it fell to under 60 percent after 15 years and to zero after 20, while a study of a Native American population found evidence of continuing protection six decades after vaccination.
Still the only vaccine of its kind
Despite that inconsistency, BCG remains the only licensed vaccine against tuberculosis a century after its introduction, and as of 2022 it was included in the vaccination schedules of 155 countries, generally those where tuberculosis remains a significant cause of illness and death. In countries such as the United States, where tuberculosis is comparatively rare, health authorities have instead relied on testing and treating latent infection rather than routine vaccination, a choice that reflects how differently BCG’s costs and benefits weigh depending on how common the disease already is in a given population. The vaccine’s continued use across most of the world, imperfect as it is, reflects the absence of any better alternative rather than confidence that the geographic variability has been resolved.
Why an imperfect vaccine still merits attention
This is worth understanding because BCG resists the tidy narrative that vaccines either clearly work or clearly do not: it has demonstrably protected people in some settings for decades, it once caused a documented, fatal disaster through contamination, and its effectiveness varies by region in ways researchers still cannot fully explain a century later. Sitting with all three facts at once, rather than reaching for whichever supports a preferred conclusion, gives a more honest picture of what a live attenuated vaccine can and cannot guarantee. An hour spent on BCG’s history is a useful corrective for anyone inclined to expect a single clean number from any vaccine.