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 Guerin (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 sub-cutaneously (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 Guerin. Calmette was a student of the eminent French microbiologist Louis Pasteur at Pasteur’s Institute in Paris. Guerin was a veterinarian who joined Calmette’s laboratory in 1897. At Lille, Calmette and Guerin 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 Guerin 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 Guerin 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 Guerin 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 Guerin 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-Guerin” (BCG).
In 1922, they began BCG-vaccinating newborn children against tuberculosis at the Charite Hospital in Paris. The immunized children exhibited no ill effects from the BCG vaccination. Calmette and Guerin’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 BCG-vaccinated 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); Salvarsan; Typhus vaccine; Yellow fever vaccine.
