Léon Charles Albert Calmette
- Bacillus Calmette-Guérin vaccine
- BCG - Bacille bilié de Calmette-Guérin
- Calmette and Wolff-Eisner ophthalmo reaction
- Calmette's serum
Biography of Léon Charles Albert Calmette
Léon Charles Albert Calmette commenced his education at the Naval Academy. However, he fell sick with typhus and had to quit, and in 1881 he decided upon a career in medicine. His dream of the Navy persevered, however, and he went to the School of Naval Physicians in Brest. Already as a student he made himself a topic as he, among other things, developed an atomizer for antiseptic solutions.
Sailor and doctor
He began his practical training in the Navy in 1883. His first station as a member of the Naval Medical Corps was Hong Kong, where he made the acquaintance of Patrick Manson (1844-1922) and became familiar with Manson's studies of the agent of malaria and translated it into French. Calmette's dissertation in 1886 discussed this theme. Now doctor of medicine, he went to West Africa, where he investigated malaria, sleeping sickness and pellagra.
Two years later he was back in France, and was later sent to Newfoundland. In 1890 he went back to Paris, and now his systematic engagement in microbiology commenced. He attended a course at the Institut Pasteur and from his teacher, Pierre Paul Emil Roux (1853-1933), soon received the assignment to establish an immunisation institute against smallpox and rabies in the Pasteur-Institute of Saigon. He devoted himself to this task from 1891. Besides this, he did research on snake poisons, plant poisons, curare, and bee poison.
During his examinations of the alcoholic fermentation of rice he found a mushroom to be the pathogen, and named it Roux it in honour of his teacher. Following a period of severe dysentery Calmette returned to France. Again he was active at the Institut Pasteur and simultaneously developed serums against different snake poisons - Calmette's serum - and took part in the development of an anti-pest serum.
The established scientist
In 1895 Roux entrusted him with the directorship of the Institut Pasteur in Lille, a position he held until 1919, nearly twenty-five years. Under his leadership this institute attainted great importance. In Lille he founded the Dispensaire antituberculeux E. Roux and assumed the chair of hygiene.
In 1899 Calmette, among others, was sent to Portugal, where an epidemic of bubonic plague threatened to spread. A year later he resumed his research in tuberculosis. He was an advocate of special healing institutions, of which the first was opened in 1905, he advocated prophylaxis and the training of specialist nurses, besides searching for a vaccine. Robert Koch's treatment with tuberculin had proved a disappointment.
Calmette resigned from his chair as teacher of bacteriology and hygiene in Lille, to devote himself completely to research on tuberculosis. In 1916 (1917?), following the death of Metchnikov, he was made vice-president of the Institut Pasteur in Paris, but was unable to leave northern France, which was occupied by the Germans (Mme. Calmette had been deported).
The development of the BCG vaccine
In his epoch-making work to develop a vaccine against tuberculosis, Calmette received important help from the veterinarian and vaccine researcher Camille Guérin. As early as in 1906 Guérin had demonstrated that resistance against tuberculosis is associated with the presence of living tubercle bacilli in the blood.
In 1908 Calmette demonstrated on cattle that small doses of injected bovine bacilli produce accumulations in the mesenterium, and that this did not cause disease. He concluded that the virulence of these bacilli was attenuated when they were cultivated on a substrate containing bile. In a communication dated December 28, 1908, Calmette informed the French Academy of Sciences of his discovery. After this Calmette and Guérin could start their historical series of experiments at the Pasteur Institute in Lille. Over a period of 13 years, from 1908 to 1921, Guérin and Calmette produced ever less virulent subcultures by cultivating bovine tubercle bacilli over and over again.
By 1921 the two researches believed they hade developed a bacillus harmless to man, yet with the ability to stimulate the production of antibodies. The vaccine was first used on newborn infants at the Charité hospital in Paris. This first vaccination was successful, and from 1924 vaccination of newborns was practiced to a large extent.
However, in 1930 the vaccination programme suffered a gruesome setback in what has become known as the Lübeck disaster. In Lübeck 73 out of 259 children vaccinated between the end of February and the beginning of April died of tuberculosis, causing serious doubt about the use of the vaccine. It was due to the efforts of the German bacteriologists Bruno Lange (born 1885) and Ludwig Lange (born 1873) that the truth was revealed: due to sloppy production the vaccine had contained virulent bacilli. It was soon proved, however, that such dangers could be eliminated through correct production methods, and in 1932 the court declared the vaccination safe.
After all such questions about the vaccine had been clarified, programmes of mass vaccination were conducted in Japan, Russia, China, England, France, Canada, and several other countries. In 1950 the University of Illinois and Research Institute obtained a licence to produce, distribute and sell the vaccine in the U.S.A. Although the vaccine was early used to a large extent on the Continent, it was not until 1956, following extensive research, that its prophylactic effect was accepted and the vaccine became commonly used in the U.S.A and Great Britain. In the U.S.A. the resistance against the use of the BCG vaccine remained strong, and it is still not used routinely.
Important Norwegian contribution
It was probably the Norwegian physician Kristian Feyer Andvord (1855-1934) who suggested to Calmette the idea of producing successively less virulent tubercle bacilli on a medium to which was added ox bile.
In 1991, in his gala lecture at the 100th anniversary of the Veterinary Institute (Veterinærinstituttet) in Oslo, Norway, "The tuberculin – a scratch through the last hundred years of medical history", chief physician Gunnar Bjune said:
"In Norway it had been noticed that contact with tuberculous cows gave slight positive tuberculin reactions, and it was speculated that this gave some degree of immunity – if the infection did not develop into glandular tuberculosis. Andvord, on of the great Norwegian experts on tuberculosis in this century, discussed this with Calmette in Paris. In 1914 the result was on the table. After a sustained period of cultivation on media containing ox bile, the bacilli had lost their ability to produce disease in cows. Could this now safely be used as a vaccine for humans?
Today it is difficult to understand that such a wild idea could be put into practice. Mildly said, the basis was thin. The safety of such a procedure had not been elucidated. Despite this, Norwegian tuberculosis experts were eager to begin testing the new vaccine. Heimbeck's vaccination tests on nurses at Ullevål in 1926 proved 80% protection and is a classic in the testing of BCG. We still do not know why it works or why it does not work som others places in the world. But it has not solved the world's health problem."
The Norwegian physician Johannes Heimbeck (1892-1976) became internationally known for his work on BCG-vaccination against tuberculosis. It was Kristian Feyer Andvord who coined the term "tuberculosis immunity" – to the horror of infection pathologists. The BCG vaccine is based on such immunity. It was the German physician Johann Lukas Schönlein who, in 1839, introduced the term tuberculosis. It was derived from the word "tubercle", first used in a thesis at the Uppsala University in 1628, then in 1689 by the English physician Richard Morton (1637-1698), to describe the characteristic lesions of consumption.
BCG is effective for both animals and man because tubercle bacilli of the bovine and human types are sufficiently related that they can produce cross-immunity. In addition, BCG is a safe vaccine because the live bacilli it contains remain at low virulence.
Besides his tuberculosis research, Calmette undertook important works to improve the water hygiene in Lille and contributed important research in the fight against ankylostomiasis.
We thank Lars-Gösta Wiman, MD, Sweden, for information submitted.