057 - The Progress of Work on Calmette's BCG Vaccine

The Lancet published an editorial in 1931 summarizing the different opinions about Calmette's BCG vaccine against tuberculosis. TB is a serious disease, so having a vaccine would be great, but not everyone agreed that the BCG was that great.

Calmette and those who supported him claimed the BCG was safe and effective. According to Calmette, 336,000 children in France and >1 million worldwide had been given the BCG over 5 years, and this had reduced mortalities from TB from 15.9% to 3.4% in children under 5. Even Calmette recognized that the BCG didn't provide permanent immunity, but he thought it was good enough to get children through the period of life where risk from TB is highest, in the early years.

Additionally, BCG supporters claimed that these bacteria, though still alive when used in vaccines, were safe and innocuous. They could produce lesions, sure, but no serious cases of tuberculosis. Many did animal studies that agreed with this claim.

On the other hand, many other medical practitioners and researchers found the claims more questionable. According to studies in cattle, guinea pigs, and monkeys, the BCG didn't seem that reliable in terms of safety or efficacy. Some of them thought they found animals dead from TB after inoculating with BCG, and some thought the BCG bacteria might increase in their virulence (ability to cause disease) after being grown in animals for long enough. And even previous studies on this blog found that Calmette's recommendations (feeding newborns BCG) didn't seem to work well, at least in animals (056).

So health professionals in Britain set up a special investigation of BCG, with not-great results. They decided that Calmette's good results could've been due to fallacies and biases and inadequate controls; for example, without blinding and placebo, it's possible that receiving the vaccine could've correlated with better care of the children in general, maybe because only cautious parents volunteered for the study or something. So hard to conclude anything. Also, some animal studies seemed to say it wasn't good, while others that it was.

Also there was a tragedy around this time in Lübeck, Germany. Many infants, 251, received BCG vaccine from the Pasteur Institute, but 67 of these soon died from tuberculosis. It turned out that what probably happened was some virulent Mycobacterium tuberculosis had been mixed with the BCG by accident. It was an awful thing that stresses the need for quality control. But it was interesting to see how different people interpreted it in different ways: some that BCG should not be used because of a risk of this kind of thing happening with any live attenuated vaccine (which makes some sense; if you don't have a good way to distinguish between strains, you can't test for contamination); and others (including Calmette) that this just shows that BCG was safe, because it was the fault of some contaminant, not the BCG itself.

But nevertheless, the Britain committee decided at this point that the BCG was still in the experimental phase, not ready for widespread use.

Citation: The Progress of Work on Calmette’s BCG Vaccine. The Lancet 218, 259–261 (1931).