Tuberculosis vaccine

The invention: 

Vaccine that uses an avirulent (nondisease) strain
of bovine tuberculosis bacilli that is safer than earlier vaccines.


The people behind the invention:

Albert Calmette (1863-1933), a French microbiologist
Camille Guérin (1872-1961), a French veterinarian and
microbiologist
Robert Koch (1843-1910), a German physician and
microbiologist





Isolating Bacteria

Tuberculosis, once called “consumption,” is a deadly, contagious
disease caused by the bacterium Mycobacterium tuberculosis,
first identified by the eminent German physician Robert Koch in
1882. The bacterium can be transmitted from person to person by
physical contact or droplet infection (for example, sneezing). The
condition eventually inflames and damages the lungs, causing difficulty
in breathing and failure of the body to deliver sufficient oxygen
to various tissues. It can spread to other body tissues, where
further complications develop.Without treatment, the disease progresses,
disabling and eventually killing the victim. Tuberculosis
normally is treated with a combination of antibiotics and other
drugs.
Koch developed his approach for identifying bacterial pathogens
(disease producers) with simple equipment, primarily microscopy.
Having taken blood samples from diseased animals, he would
identify and isolate the bacteria he found in the blood. Each strain of
bacteria would be injected into a healthy animal. The latter would
then develop the disease caused by the particular strain.
In 1890, he discovered that a chemical released from tubercular
bacteria elicits a hypersensitive (allergic) reaction in individuals
previously exposed to or suffering from tuberculosis. This chemical,
called “tuberculin,” was isolated from culture extracts in which tubercular
bacteria were being grown.
When small amounts of tuberculin are injected into a person subcutaneously
(beneath the skin), a reddened, inflamed patch approximately
the size of a quarter develops if the person has been exposed
to or is suffering from tuberculosis. Injection of tuberculin into an
uninfected person yields a negative response (that is, no inflammation).
Tuberculin does not harm those being tested.



Tuberculosis’s Weaker Grandchildren


The first vaccine to prevent tuberculosis was developed in 1921
by two French microbiologists, Albert Calmette and Camille Guérin.
Calmette was a student of the eminent French microbiologist Louis
Pasteur at Pasteur’s Institute in Paris. Guérin was a veterinarian
who joined Calmette’s laboratory in 1897. At Lille, Calmette and
Guérin focused their research upon the microbiology of infectious
diseases, especially tuberculosis.
In 1906, they discovered that individuals who had been exposed to
tuberculosis or who had mild infections were developing resistance to
the disease. They found that resistance to tuberculosis was initiated by
the body’s immune system. They also discovered that tubercular bacteria
grown in culture over many generations become progressively
weaker and avirulent, losing their ability to cause disease.
From 1906 through 1921, Calmette and Guérin cultured tubercle
bacilli from cattle. With proper nutrients and temperature, bacteria
can reproduce by fission (that is, one bacterium splits into two bacteria)
in as little time as thirty minutes. Calmette and Guérin cultivated
these bacteria in a bile-derived food medium for thousands of
generations over fifteen years, periodically testing the bacteria for
virulence by injecting them into cattle. After many generations, the
bacteria lost their virulence, their ability to cause disease. Nevertheless,
these weaker, or “avirulent” bacteria still stimulated the animals’
immune systems to produce antibodies. Calmette and Guérin
had successfully bred a strain of avirulent bacteria that could not
cause tuberculosis in cows but could also stimulate immunity against
the disease.
There was considerable concern over whether the avirulent strain
was harmless to humans. Calmette and Guérin continued cultivating
weaker versions of the avirulent strain that retained antibody-
stimulating capacity. By 1921, they had isolated an avirulent antibody-
stimulating strain that was harmless to humans, a strain they
called “Bacillus Calmette-Guérin” (BCG).
In 1922, they began BCG-vaccinating newborn children against
tuberculosis at the Charité Hospital in Paris. The immunized children
exhibited no ill effects from the BCG vaccination. Calmette and
Guérin’s vaccine was so successful in controlling the spread of tuberculosis
in France that it attained widespread use in Europe and
Asia beginning in the 1930’s.

Impact

Most bacterial vaccines involve the use of antitoxin or heat- or
chemical-treated bacteria. BCG is one of the few vaccines that use
specially bred live bacteria. Its use sparked some controversy in
the United States and England, where the medical community
questioned its effectiveness and postponed BCG immunization
until the late 1950’s. Extensive testing of the vaccine was performed
at the University of Illinois before it was adopted in the
United States. Its effectiveness is questioned by some physicians to
this day.
Some of the controversy stems from the fact that the avirulent,
antibody-stimulating BCG vaccine conflicts with the tuberculin
skin test. The tuberculin skin test is designed to identify people
suffering from tuberculosis so that they can be treated. A BCGvaccinated
person will have a positive tuberculin skin test similar
to that of a tuberculosis sufferer. If a physician does not know that
a patient has had a BCG vaccination, it will be presumed (incorrectly)
that the patient has tuberculosis. Nevertheless, the BCG
vaccine has been invaluable in curbing the worldwide spread of
tuberculosis, although it has not eradicated the disease.


See also:

Antibacterial drugs; Birth control pill; Penicillin; Polio vaccine (Sabin);
Polio vaccine (Salk)