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Goodpasture’s 1919 Article on the Etiology of Influenza
HISTORICAL PERSPECTIVE
Goodpasture’s 1919 Article on the Etiology of Influenza Harold M. Henderson, MD
Key Indexing Terms: Goodpasture; Influenza; Pandemic. [Am J Med Sci 2009;338(2):152–153.]
E
rnest W. Goodpasture (1886 –1960) had a long and distinguished academic medical career. After completing his medical school training at Johns Hopkins, he was a member of the resident staff in pathology at Johns Hopkins and then at the Peter Bent Brigham Hospital and Harvard Medical School during the period 1913–1918. His initial academic position was as Assistant Professor of Pathology at Harvard beginning in 1918, and he ultimately became chief of the Department of Pathology at the Vanderbilt School of Medicine in 1925. He remained chief of pathology at Vanderbilt until his retirement in 1955 and also served as Dean of the Medical School during some of that time period.1 Today, he is best known for his method of growing uncontaminated viruses in chick embryos and for the syndrome that still bears his name: Goodpasture’s syndrome, referring to a disease caused by antiglomerular basement membrane antibodies. Less well known, but no less important, are his descriptions of the pathologic appearance of influenza pneumonia and his contributions to the investigation into the etiologic agent of influenza, which took place during the 1918 –1919 pandemic. In 1918, in addition to his academic position at Harvard, Goodpasture was employed in the United States Navy Medical Service and was a pathologist at the Chelsea Naval Hospital near Boston.2 He conducted postmortem examinations on multiple influenza victims, starting from the earliest stages of the pandemic and extending on through the peak months in the fall of 1918 into the early part of 1919. He discussed his findings and their implications in a series of articles published in 1919,3,4 culminating with the article “The significance of certain pulmonary lesions in relation to the etiology of influenza” originally published in the December 1919 issue of The American Journal of the Medical Sciences,5 and reprinted in the current issue of The American Journal of the Medical Sciences. At the time of 1918 –1919 pandemic, it was widely believed within the medical community that the cause of influenza was something known as Bacillus influenzae or “Pfeiffer’s bacillus.” During the previous major influenza pandemic of 1889 –1990, the influential German physician Richard Pfeiffer had isolated this organism (today known as Hemophilus influenzae) from multiple patients with influenza. Although the disease produced by the organism in animal models was not identical to human influenza, Pfeiffer’s belief that it was indeed the etiologic agent took firm root among many of the medical scientists of the era.6 Goodpasture doubted this claim and undertook a detailed study of the pathologic specimens available to him. His were
among the earliest and most detailed descriptions of the typical pulmonary lesions of human influenza. The pulmonary lesion to which I would especially refer is a dilated condition of alveolar ducts, with a hyaline membrane partially or completely covering their walls and sometimes those of subtended alveoli . . . The membrane is not present within all dilated air spaces and is not uniformly distributed throughout the lung. It may be most conspicuous in areas of the lung that contain least exudate. It is present most conspicuously in acute pneumonia of short duration accompanying influenza.5
Goodpasture isolated Pfeiffer’s bacillus in some of the specimens he cultured, but it was absent in many others, and the pneumococcus and other streptococci were often isolated instead. He stated his conclusion that the cause of influenza was not bacterial. The great variations in the results of bacteriologic analyses of the lungs and respiratory tract of those dead of influenza have left no common ground for agreement on any one microorganism as the etiologic agent of this disease. Although in certain sections of the country evidence seemed to be strongly in favor of Pfeiffer’s bacillus, the failure to find this microorganism and the predominance of other invading bacteria in different localities have served in large measure to counteract what early seemed to be a confirmation of Pfeiffer’s view . . . I am convinced that . . . the etiologic factor is not any one of the numerous pathogenic microorganisms that have been cultivated from the lungs, often in pure culture, but an unknown virus, which produces the general intoxication and may produce characteristic lesions in the lungs with or without the coincidence of other infectious agents.5
It would take more than another decade before Goodpasture’s hypothesis was proven correct. In 1931, the swine influenza virus was isolated and shown to be capable of transmitting the disease to healthy pigs,7,8 and in 1933 a series of experiments involving the first successful transmission of a human influenza virus to ferrets fulfilled Koch’s postulates and confirmed a virus as the etiologic agent of human influenza.9 More recently, the genetic sequence of the original 1918 H1N1 pandemic viral strain, whose victims were studied by Goodpasture 90 years ago, has been fully characterized and shown to be that of a highly virulent pandemic virus,10,11 bringing us full circle and allowing us to appreciate Goodpasture’s achievement of 1918 –1919. REFERENCES
From the Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi. Correspondence: Harold M. Henderson, MD, Division of Infectious Diseases, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216 (E-mail: [email protected]).
152
1. Ernest W. Goodpasture Papers, Eskind Biomedical Library, Vanderbilt University Medical Center. 2. Crosby A. Epidemic and peace, 1918. Westport (CT): Greenwood Press; 1976.
The American Journal of the Medical Sciences • Volume 338, Number 2, August 2009
Etiology of Influenza
3. Goodpasture EW, Burnett FL. The pathology of pneumonia accompanying influenza. US Naval Med Bull 1919;13:177–97.
8. Shope RE. Swine influenza. III. Filtration experiments and etiology. J Exp Med 1931;54:373– 85.
4. Goodpasture EW. Bronchopneumonia due to hemolytic streptococci following influenza. JAMA 1919;72:724 –5.
9. Smith W, Andrewes CH, Laidlaw PP. A virus obtained from influenza patients. Lancet 1933;2:66 – 8.
5. Goodpasture EW. The significance of certain pulmonary lesions in relation to the etiology of influenza. Am J Med Sci 1919;158: 863–70.
10. Taubenberger JK, Reid AH, Krafft AE, et al. Initial characterization of the 1918 “Spanish” influenza virus. Science 1997;275: 1793– 6.
6. Barry J. The great influenza. New York: Viking Penguin; 2004.
11. Tumpey TM, Basler CF, Aguilar PV, et al. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005; 310:77– 80.
7. Shope RE. Swine influenza. I. Experimental transmission and pathology. J Exp Med 1931;54:349 –59.
© 2009 Lippincott Williams & Wilkins
153
Goodpasture’s 1919 Article on the Etiology of Influenza Harold M. Henderson, MD
Key Indexing Terms: Goodpasture; Influenza; Pandemic. [Am J Med Sci 2009;338(2):152–153.]
E
rnest W. Goodpasture (1886 –1960) had a long and distinguished academic medical career. After completing his medical school training at Johns Hopkins, he was a member of the resident staff in pathology at Johns Hopkins and then at the Peter Bent Brigham Hospital and Harvard Medical School during the period 1913–1918. His initial academic position was as Assistant Professor of Pathology at Harvard beginning in 1918, and he ultimately became chief of the Department of Pathology at the Vanderbilt School of Medicine in 1925. He remained chief of pathology at Vanderbilt until his retirement in 1955 and also served as Dean of the Medical School during some of that time period.1 Today, he is best known for his method of growing uncontaminated viruses in chick embryos and for the syndrome that still bears his name: Goodpasture’s syndrome, referring to a disease caused by antiglomerular basement membrane antibodies. Less well known, but no less important, are his descriptions of the pathologic appearance of influenza pneumonia and his contributions to the investigation into the etiologic agent of influenza, which took place during the 1918 –1919 pandemic. In 1918, in addition to his academic position at Harvard, Goodpasture was employed in the United States Navy Medical Service and was a pathologist at the Chelsea Naval Hospital near Boston.2 He conducted postmortem examinations on multiple influenza victims, starting from the earliest stages of the pandemic and extending on through the peak months in the fall of 1918 into the early part of 1919. He discussed his findings and their implications in a series of articles published in 1919,3,4 culminating with the article “The significance of certain pulmonary lesions in relation to the etiology of influenza” originally published in the December 1919 issue of The American Journal of the Medical Sciences,5 and reprinted in the current issue of The American Journal of the Medical Sciences. At the time of 1918 –1919 pandemic, it was widely believed within the medical community that the cause of influenza was something known as Bacillus influenzae or “Pfeiffer’s bacillus.” During the previous major influenza pandemic of 1889 –1990, the influential German physician Richard Pfeiffer had isolated this organism (today known as Hemophilus influenzae) from multiple patients with influenza. Although the disease produced by the organism in animal models was not identical to human influenza, Pfeiffer’s belief that it was indeed the etiologic agent took firm root among many of the medical scientists of the era.6 Goodpasture doubted this claim and undertook a detailed study of the pathologic specimens available to him. His were
among the earliest and most detailed descriptions of the typical pulmonary lesions of human influenza. The pulmonary lesion to which I would especially refer is a dilated condition of alveolar ducts, with a hyaline membrane partially or completely covering their walls and sometimes those of subtended alveoli . . . The membrane is not present within all dilated air spaces and is not uniformly distributed throughout the lung. It may be most conspicuous in areas of the lung that contain least exudate. It is present most conspicuously in acute pneumonia of short duration accompanying influenza.5
Goodpasture isolated Pfeiffer’s bacillus in some of the specimens he cultured, but it was absent in many others, and the pneumococcus and other streptococci were often isolated instead. He stated his conclusion that the cause of influenza was not bacterial. The great variations in the results of bacteriologic analyses of the lungs and respiratory tract of those dead of influenza have left no common ground for agreement on any one microorganism as the etiologic agent of this disease. Although in certain sections of the country evidence seemed to be strongly in favor of Pfeiffer’s bacillus, the failure to find this microorganism and the predominance of other invading bacteria in different localities have served in large measure to counteract what early seemed to be a confirmation of Pfeiffer’s view . . . I am convinced that . . . the etiologic factor is not any one of the numerous pathogenic microorganisms that have been cultivated from the lungs, often in pure culture, but an unknown virus, which produces the general intoxication and may produce characteristic lesions in the lungs with or without the coincidence of other infectious agents.5
It would take more than another decade before Goodpasture’s hypothesis was proven correct. In 1931, the swine influenza virus was isolated and shown to be capable of transmitting the disease to healthy pigs,7,8 and in 1933 a series of experiments involving the first successful transmission of a human influenza virus to ferrets fulfilled Koch’s postulates and confirmed a virus as the etiologic agent of human influenza.9 More recently, the genetic sequence of the original 1918 H1N1 pandemic viral strain, whose victims were studied by Goodpasture 90 years ago, has been fully characterized and shown to be that of a highly virulent pandemic virus,10,11 bringing us full circle and allowing us to appreciate Goodpasture’s achievement of 1918 –1919. REFERENCES
From the Department of Medicine, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, Mississippi. Correspondence: Harold M. Henderson, MD, Division of Infectious Diseases, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216 (E-mail: [email protected]).
152
1. Ernest W. Goodpasture Papers, Eskind Biomedical Library, Vanderbilt University Medical Center. 2. Crosby A. Epidemic and peace, 1918. Westport (CT): Greenwood Press; 1976.
The American Journal of the Medical Sciences • Volume 338, Number 2, August 2009
Etiology of Influenza
3. Goodpasture EW, Burnett FL. The pathology of pneumonia accompanying influenza. US Naval Med Bull 1919;13:177–97.
8. Shope RE. Swine influenza. III. Filtration experiments and etiology. J Exp Med 1931;54:373– 85.
4. Goodpasture EW. Bronchopneumonia due to hemolytic streptococci following influenza. JAMA 1919;72:724 –5.
9. Smith W, Andrewes CH, Laidlaw PP. A virus obtained from influenza patients. Lancet 1933;2:66 – 8.
5. Goodpasture EW. The significance of certain pulmonary lesions in relation to the etiology of influenza. Am J Med Sci 1919;158: 863–70.
10. Taubenberger JK, Reid AH, Krafft AE, et al. Initial characterization of the 1918 “Spanish” influenza virus. Science 1997;275: 1793– 6.
6. Barry J. The great influenza. New York: Viking Penguin; 2004.
11. Tumpey TM, Basler CF, Aguilar PV, et al. Characterization of the reconstructed 1918 Spanish influenza pandemic virus. Science 2005; 310:77– 80.
7. Shope RE. Swine influenza. I. Experimental transmission and pathology. J Exp Med 1931;54:349 –59.
© 2009 Lippincott Williams & Wilkins
153