Interventions for Tuberculosis Control and Elimination 2002

too small to allow a meaningful interpretation of the efficacy of this vaccination.
The method never gained much attention beyond Germany, and
fell into oblivion as vaccination with BCG drew increasing attention in the
immediately succeeding years.
Vaccination with BCG
Vaccine development
A virulent strain of M. bovis, isolated by Nocard in 1902, from milk obtained
from a cow with tuberculous mastitis 655 was inoculated for the first time
on January 8, 1908, by Albert Calmette (1863-1933) and Camille Guérin
(1872-1961) 656 at the Pasteur Institute in Lille, France 657 onto a medium
consisting of cooked potato and glycerinated bile.
The strain, to become known as Bacille Calmette-Guérin (BCG), was
sub-cultured in 230 passages on bile potato medium until 1921 when it no
longer changed its characteristics.
After thirty passages the strain ceased to kill guinea pigs; after sixty
it was still slightly virulent for rabbits and horses, but avirulent for guineapigs,
monkeys, and calves. 655 From 1912 onwards, experiments were conducted
among calves, demonstrating their resistance to subsequent infection
with virulent bacilli. 655 It may be noted that the main objective in the
development of this vaccine was to obtain an effective vaccine against tuberculosis
in goats 658 and cattle. 658,659 It is now clear that it was not the glycerinated
bile medium that was the reason for the loss of virulence. 660,661
By sub-culturing four bovine strains on Calmette’s bile-potato medium over
six years, Griffith failed to reproduce Calmette’s finding and to induce stable
attenuation. 662 The reasons for the loss of virulence of M. bovis BCG
remain unclear until today.
On July 1, 1921, Weill-Hallé, a pediatrician, requested the vaccine for
use in an infant born to a mother who had died of tuberculosis shortly after
delivery. The child was to be brought up by a grandmother who was herself
suffering from tuberculosis. 663 The child was given 6 mg of BCG
orally and developed normally over the next six months without any sign
of illness, either from the vaccine or from tuberculosis. 655,663 Over the next
three years, 317 infants (67 of whom were born into, and brought up by
families with tuberculosis patients) were vaccinated with 30 mg oral BCG
vaccine, given in three portions at 48-hour intervals.
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