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INT J TUBERC LUNG DIS 9(9):944–945
© 2005 The Union
Leon Charles Albert Calmette and BCG vaccine
T. M. Daniel
Department of Medicine, Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA
ALBERT CALMETTE is known throughout the world
today because his name is attached to the widely used
vaccine against tuberculosis (TB). With his associate,
Camille Guérin, he developed bacille Calmette-Guérin
(BCG), for which he deserves credit. He was, however, more than simply the person who attenuated
Mycobacterium bovis to produce the vaccine.
Calmette was born on 12 July 1863 in Nice,
France.1 At age 10, he moved with his family to Brest,
where he suffered typhoid during an outbreak that
swept through the lycée in which he was enrolled. Unable to join the French navy as a regular mariner because of his typhoid history, he entered the Naval
Medical College of Brest in 1881. He earned the title
of ‘aide-médecin’ in 1883 and was sent to South-East
Asia. There he met Patrick Munson and made observations on lymphatic filariasis under Munson’s tutelage. Returning to France, he completed his medical
studies in Paris in 1886; the title of his thesis was
‘Etude critique sur la pathogénie des maladies tropicales attribuées à la filaire du sang humain’.
Calmette was then sent to the Congo, where he
spent 2 years before returning to France in 1888. In
that year he married Emilie de la Salle. After 18 months
on a French island off the coast of Newfoundland
studying a disease of cod fish, Calmette obtained an
appointment in the French Colonial Medical Service.
He secured a position at the Institut Pasteur in Paris,
where he studied the new science of bacteriology with
Émile Roux.
In 1891, on the recommendation of Pasteur, Calmette was sent to Saigon, in what was then French
Indochina, as the founding director of a newly opened
Institut Pasteur in that city.2,3 Calmette was well prepared for this position. He had already developed a
draft plan for a tropical research laboratory, and the
official documents establishing the laboratory drew
heavily upon his draft.
Shortly after his arrival in Saigon, Calmette insti-
K E Y W O R D S : Albert Calmette; BCG; tuberculosis
Figure
Albert Calmette. Drawing by Robert Conley.
tuted studies of Koch’s tuberculin treatment of TB.
He quickly concluded that tuberculin therapy produced more harm than benefit. He nevertheless went
on to try tuberculin for the treatment of leprosy, again
with disastrous results. French troops in the region
were plagued with recurrent dysentery, and Calmette
conducted a number of studies trying to establish a
bacterial etiology. He focused on a Pseudomonas species that he isolated from the blood and colonic ulcers
of persons who had succumbed to diarrheal disease.
He conducted meticulous animal studies, but was unable to satisfy himself that the organism was the cause
of tropical dysentery. Calmette was more successful
in dealing with rabies and venomous snake bites. He
established a laboratory for the production of Pasteur’s rabies vaccine using rabbit spinal cords, and he
developed an antisnake venom serum.
Disabled by dysentery, Calmette returned to Paris
and the Institut Pasteur in 1893. There he continued
his work on snake venom, developing a polyvalent
antivenom. He himself was bitten while handling a
Correspondence to: Prof Thomas M Daniel, Department of Medicine, Center for Global Health and Diseases, Case Western
Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-7286, USA. Tel: (11) 216-368-6321. Fax: (11) 216-3684825. e-mail: tmd5@cwru.edu
[A version in French of this article is available from the Editorial Office in Paris and from the Union website www.iuatld.org]
Acquisition of drug resistance in MDR-TB
snake and was treated with his serum. He recovered,
but lost the tip of his right index finger.
Recognition and fame came to Calmette. He was
made a Chevalier of the Légion d’Honneur in 1893.
He was elected to the French Academy of Science in
1907 and to the Academy of Medicine in 1919. In
1920 he presided over the first meeting of the International Union Against Tuberculosis.
When the city of Lille raised money to establish a
new branch of the Institut Pasteur in 1895, Calmette
was chosen as its director. He recognized TB as the
city’s major health problem; the TB death rate was
approximately 300/100 000 population/year. Calmette
decided that his work in the new institute would focus on this disease. He opened a TB clinic in 1891, the
first such clinic in France, and France’s first public TB
hospital in 1905. He had not completely abandoned
the tropical world, however, and in 1912 he published an analysis of tuberculin reactivity in several
French colonies based on data received from those
areas.4
Calmette was joined by Guérin in 1897, and together they began the work that would lead to BCG.5,6
They obtained a culture of M. bovis from Edmond
Nocard in Paris; he had isolated the organism from
the udder of a tuberculous cow in 1902. Frustrated by
clumping of organisms in their liquid medium cultures,
they added ox bile to their culture medium in 1908.
Not only did this promote more dispersed growth,
but for the first time a substantial decrease in the virulence of the organism for guinea pigs was noted in
subsequent passages. More than 200 passages in cultures and laboratory animals followed, and in 1913
they were ready to inject the now attenuated M. bovis
into cows for evaluation as a protective vaccine.
War erupted in Europe, and German armies swept
across northern France, laying siege to Lille. After 10
days of nearly constant artillery shelling, the city fell
to the invaders. Nine cows had been vaccinated and
then challenged with virulent M. bovis. The Germans
requisitioned the animals for slaughter to feed their
soldiers, but with the collusion of veterinarians of the
invading forces, Calmette and Guérin were able to
autopsy the animals. None had TB. As the war continued, the Germans began taking civilian hostages.
On 12 January 1918, Calmette’s wife was sent to
be interned in Germany until 1919, after the end of
the war.
In June 1919, Calmette was recalled to Paris to
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become deputy director of the Institut Pasteur. Guérin
joined him there, and they continued their work with
BCG. Two years later they were ready to give their
vaccine to a human. They collaborated with Drs Benjamin Weill-Hallé and Raymond Turpin at the Hôpital Charité in Paris, and in July 1921, they gave 6 mg
of BCG orally to a 3-day-old infant whose mother
had died of pulmonary TB (PTB) the day following
the birth. The baby was to be placed in the care of its
grandmother, who had smear-positive PTB. Additional doses of BCG were given on the fifth and seventh
day of the infant’s life. When examined at 6 months,
the child was well and showed no signs of TB, despite
being almost constantly exposed to its grandmother.
Cautiously, Calmette and his colleagues gave BCG
to additional children, including his own grandchildren. By 1928 more than 100 000 doses had been
given and the vaccine had become accepted. In the
spring of 1930 in what Calmette called ‘le catastrophe
de Lübeck’, 251 young children were mistakenly
given virulent cultures of M. tuberculosis instead of
BCG. Sixty-seven died of TB. Others were less seriously afflicted, but only 72 remained healthy. Calmette himself led the investigation of the incident.7
Despite exoneration of the vaccine, this incident dramatically slowed acceptance of BCG. Not until the
vaccination campaigns led by Johannes Holm in postWorld War II Europe was BCG again widely accepted.
Calmette never recovered his optimism and cheerful disposition after the Lübeck disaster. He continued
to work at the Institut Pasteur, and became increasingly preoccupied with the rise of German Naziism.
He died on 29 October 1933 at the age of 70.
References
1 Sakula A. BCG: who were Calmette and Guérin? Thorax 1983;
38: 806–812.
2 Gelinas J A. Albert Calmette. The Saigon years 1891–1893: a
historical review. Mil Med 1973; 138: 730–733.
3 Guénel A. The creation of the first overseas Pasteur Institute, or
the beginning of Albert Calmette’s Pastorian career. Med Hist
1999; 43: 1–25.
4 Calmette A. Enquète sur l’épidémiologie de la tuberculose dan
les colonies françaises. Ann Inst Pasteur 1912; 26: 497–514.
5 Daniel T M. Captain of death: the story of tuberculosis. Rochester, NY: University of Rochester Press, 1997.
6 Moore D F. The history and development of the BCG. Practitioner 1983; 227: 1–3.
7 Calmette A. Épilogue de la catastrophe de Lübeck. Presse Méd
1931; 39: 17–18.