Pediatric Annals

FROM THE GUEST EDITOR 

The History of the Pneumococcus

Stanford T Shulman, MD

Abstract

In the second half of 1880, two remarkable scientists independently discovered the lancet-shaped diplococcal microbe that we now know as Streptococcus pneumoniae, or the pneumococcus. George Miller Sternberg, working for the U.S. Army in New Orleans on the etiology of malaria in the autumn of 1880, injected his own saliva subcutaneously into rabbits as controls. Fatal sepsis with paired cocci was observed. He reported this in 1881(1) and named the organism Micrococcus pasteuri to honor Louis Pasteur. Shortly after Sternberg's experiment, Pasteur isolated the same organism in December 1880 after injecting rabbits with saliva of an infant who died of hydrophobia (rabies) in Paris. Pasteur published his report 3 months before Sternberg's and referred to this organism initially as Microbe septicemique du salive.2

The details of Pasteur's career are widely known, but Sternberg (1838-1915) warrants recognition as America's most prominent early bacteriologist. His distinguished career included graduation in 1860 from the College of Physicians and Surgeons of New York and service as a surgeon in the Civil War. He was captured at the Battle of Bull Run, but then escaped. For several decades, he performed pioneering research in the new field of bacteriology and published a Manual of Bacteriology in 1893. Ultimately, he was named Brigadier General and Surgeon General of the Army, serving from 1893 to 1902. During this period, he established the Army Medical School in 1893, organized the Army Nurse Corps, the Typhoid Fever Board, and the Yellow Fever Commission (the latter two involving Major Walter Reed), and solved the medical problems associated with the Spanish-American War.

Prior to Sternberg's and Pasteur's isolation of the pneumococcus in the laboratory, the organism probably had been visualized in pulmonary tissue as early as 1875 by Klebs, by Eberth in 1880, and by the great Robert Koch in 1880 or 1881 .3 After considerable initial controversy, this organism was shown to be a major cause of pneumonia during the 1880s. It was also established during that decade that the pneumococcus caused bacteremia, meningitis, otitis media, and septic arthritis.3

The pneumococcus played a crucial role in several fundamental biologic discoveries during the subsequent century. For example, the initial report of the Gram stain in 1884 included description of many pairs of slightly elongated cocci that retained the violet stain (ie, that were Gram positive) in lung sections.4 The pneumococcus was the organism used to document that, following animal immunization, immune serum could be protective and that it promoted uptake of organisms by phagocytes (ie, that it was opsonic).3,4 Metchnikov observed that heavily encapsulated strains were more resistant to phagocytosis in the 1890s. The relative importance of the complement system and of antibodies in promoting opsonophagocytosis of encapsulated organisms was established later in studies of the pneumococcus.

Research studies in the 1930s by Dubos and Avery proved the importance of the pneumococcal capsule to virulence, work that led to serotyping, to the science of modern quantitative immunology, and, ultimately, to the demonstration in 1944 by Avery, MacLeod, and McCarty that DNA was the material of genetic information. This provided the basis for the sciences of molecular genetics and molecular biology.5

Some of the earliest vaccine developmental efforts were those of Sir Almroth Wright in 1911.6 One of the first observations of the treatment of a specific bacterial infection (experimental pneumococcal infection of mice) with a specific antimicrobial agent (optochin) was reported in 1911. 7 This work also included the observation mat pneumococci rapidly developed resistance to this agent, the first such demonstration of the problem that today complicates our treatment of bacterial infections. When sulfonamides and penicillin were introduced, their therapeutic efficacy…

In the second half of 1880, two remarkable scientists independently discovered the lancet-shaped diplococcal microbe that we now know as Streptococcus pneumoniae, or the pneumococcus. George Miller Sternberg, working for the U.S. Army in New Orleans on the etiology of malaria in the autumn of 1880, injected his own saliva subcutaneously into rabbits as controls. Fatal sepsis with paired cocci was observed. He reported this in 1881(1) and named the organism Micrococcus pasteuri to honor Louis Pasteur. Shortly after Sternberg's experiment, Pasteur isolated the same organism in December 1880 after injecting rabbits with saliva of an infant who died of hydrophobia (rabies) in Paris. Pasteur published his report 3 months before Sternberg's and referred to this organism initially as Microbe septicemique du salive.2

The details of Pasteur's career are widely known, but Sternberg (1838-1915) warrants recognition as America's most prominent early bacteriologist. His distinguished career included graduation in 1860 from the College of Physicians and Surgeons of New York and service as a surgeon in the Civil War. He was captured at the Battle of Bull Run, but then escaped. For several decades, he performed pioneering research in the new field of bacteriology and published a Manual of Bacteriology in 1893. Ultimately, he was named Brigadier General and Surgeon General of the Army, serving from 1893 to 1902. During this period, he established the Army Medical School in 1893, organized the Army Nurse Corps, the Typhoid Fever Board, and the Yellow Fever Commission (the latter two involving Major Walter Reed), and solved the medical problems associated with the Spanish-American War.

Prior to Sternberg's and Pasteur's isolation of the pneumococcus in the laboratory, the organism probably had been visualized in pulmonary tissue as early as 1875 by Klebs, by Eberth in 1880, and by the great Robert Koch in 1880 or 1881 .3 After considerable initial controversy, this organism was shown to be a major cause of pneumonia during the 1880s. It was also established during that decade that the pneumococcus caused bacteremia, meningitis, otitis media, and septic arthritis.3

The pneumococcus played a crucial role in several fundamental biologic discoveries during the subsequent century. For example, the initial report of the Gram stain in 1884 included description of many pairs of slightly elongated cocci that retained the violet stain (ie, that were Gram positive) in lung sections.4 The pneumococcus was the organism used to document that, following animal immunization, immune serum could be protective and that it promoted uptake of organisms by phagocytes (ie, that it was opsonic).3,4 Metchnikov observed that heavily encapsulated strains were more resistant to phagocytosis in the 1890s. The relative importance of the complement system and of antibodies in promoting opsonophagocytosis of encapsulated organisms was established later in studies of the pneumococcus.

Research studies in the 1930s by Dubos and Avery proved the importance of the pneumococcal capsule to virulence, work that led to serotyping, to the science of modern quantitative immunology, and, ultimately, to the demonstration in 1944 by Avery, MacLeod, and McCarty that DNA was the material of genetic information. This provided the basis for the sciences of molecular genetics and molecular biology.5

Some of the earliest vaccine developmental efforts were those of Sir Almroth Wright in 1911.6 One of the first observations of the treatment of a specific bacterial infection (experimental pneumococcal infection of mice) with a specific antimicrobial agent (optochin) was reported in 1911. 7 This work also included the observation mat pneumococci rapidly developed resistance to this agent, the first such demonstration of the problem that today complicates our treatment of bacterial infections. When sulfonamides and penicillin were introduced, their therapeutic efficacy was noteworthy but the emergence of resistant organisms was observed, promptly with the sulfonamides and after several decades with the penicillins.

This remarkable organism that was integral to so many important scientific discoveries was first referred to as Pneumococcus by Fraenkel in 1886 in recognition of its importance in pneumonia.4 In 1920, it was renamed Diplococcus pneumoniae, and in 1974 was given its current designation as Streptococcus pneumoniae to recognize its growth as chained cocci in broth and its relationship to other streptococci.

Pasteur has been honored on many postage stamps, particularly ones issued by French-speaking countries. The red and blue-green stamp from the French Territory of Afars and Issas (you all know where that is!) highlights Pasteur's early interest in crystal formation and microbiology. Please note the chains of cocci (streptococci) at the lower left.

The brown and ochre stamp from Monaco portrays vaccination of man, sheep, and cattle, a microscope, and laboratory glassware.

The blue, yellow, and black stamp from St. Pierre and Miquelon (French islands off the coast of Canada that starred in the recent movie "The Widow of St. Pierre") honors the centennial of Pasteur's death in 1895.

REFERENCES

1. Sternberg GM. A fatal form of septicemia in the rabbit. National Board of Health Bulletin. 1881,2:781-783.

2. Pasteur L, Chamberland C, Roux E. Sur une maladie nouvelle, provoquee par la salive d'un enfant mort de la rage. Compt Rend Acad d Sci. 1881;92:159-165.

3. Austrian R. Pneumococcus: the first one hundred years. Rev Infect Dis. 1981;3:183-189.

4. Watson DA, Musher DM, Jacobson JW, Verhoef J. A brief history of the pneumococcus in biomedical research: a panoply of scientific discovery. Clin Infect Dis. 1993;17:913-924.

5. Avery OT, MacLeod CM, McCarty M. Studies on the chemical nature of the substance inducing transformation of pneumococcal types. J Exp Med. 1944;79:137-158.

6. Wright AE, Morgan WP, Colebrook L, Dodgson RW. Observations on prophylactic inoculation against pneumococcus infections. Lancet. 1914;1:1-10, 87-95.

7. Morganrom J, Levy R. Chemotherapie der Pneumokokkeninfektion. Berliner Klinische Wochenshrift. 1911,48:15601561.

10.3928/0090-4481-20020401-05

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