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Influenza: Exposing the True Killer

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Influenza: Exposing the True Killer FROM THE ARCHIVE Influenza: exposing the true killer In the early 1930s, Richard Shope isolated influenza virus from infected pigs. Shope’s finding was quickly followed by the isolation of the influenza virus from humans, proving that a virus —not a bacterium, as was widely believed— caused influenza. In 1892, German bacteriologist Richard an atypical bacterium called Bacterium Pfeiffer isolated what he thought was pneumosintes), other researchers could the causative agent of influenza. The not reproduce their results. One of the culprit, according to Pfeiffer, was a doubters was Oswald Avery (Rockefeller small rod-shaped bacterium that he Institute), who developed a culture isolated from the noses of flu-infected media—chocolate agar—that optimized patients (1). He dubbed it Bacillus influ- the growing conditions for B. influenzae enzae (or Pfeiffer’s bacillus). Few and thus minimized false negative results doubted the validity of this discovery, from patient samples. Thus, the idea in large part because bacteria had been that flu was transmitted by a filterable shown to cause other human diseases, agent (or virus) was dismissed. Rockefeller University Archive including anthrax, cholera, and plague. Richard Shope, 1936. Insights from pigs The filtration question Olitsky and Gates would not be vin- Shope published his results in a series When history’s deadliest influenza pan- dicated until a decade later, when of papers in The Journal of Experimental demic began in 1918, most scientists Shope—a young physician from Iowa Medicine (5, 6). believed that Pfeiffer’s bacillus caused then working on hog cholera at the Using Shope’s technique, Wilson influenza. With the lethality of this Rockefeller Institute—turned his at- Smith, Christopher Andrewes, and outbreak (which killed an estimated tention to swine influenza. Patrick Laidlaw (National Institute for 20 to 100 million worldwide) came Pig farmers in Iowa had reported Medical Research, UK) soon isolated urgency—researchers around the world two outbreaks—one in 1918 and an- the virus from humans (7), laying to began to search for Pfeiffer’s bacillus in other in 1929—of a highly contagious, rest any lingering doubts about the patients, hoping to develop antisera and influenza-like disease among their nature of the flu-inducing agent. vaccines that would protect against in- animals. The disease bore such a remark- Both Shope and the British trio fection. In many patients, but not all, able resemblance to human flu that it later demonstrated that sera from humans the bacteria were found. Failures to was named swine influenza. Shope and that were infected with the 1918 flu isolate B. influenzae (now known as his mentor Paul Lewis took mucus and virus could neutralize the pig virus, Haemophilus influenzae) were largely lung samples from the infected pigs and leading them to conclude that the chalked up to inadequate technique, as attempted to isolate the disease-causing swine virus was a surviving form of the the bacteria were notoriously difficult agent. They quickly isolated a bacte- 1918 human pandemic virus (8, 9). In to culture (2). rium that looked exactly like Pfeiffer’s fact, a related strain of flu still circulates The first potential blow to Pfeiffer’s human bacterium (and was thus called among pigs today. theory came from Peter Olitsky and B. influenzae suis), but when they injected Frederick Gates at The Rockefeller the bacteria into pigs, it caused no REFERENCES: Institute. Olitsky and Gates took nasal disease (5). 1. Pfeiffer, R.F.J. Deutsche medicinische secretions from patients infected with Shope then filtered the samples and, Wochenschrift. 1892. 18:28. 2. Barry, J.M. 2004. The Great Influenza. the 1918 flu and passed them through like Olitsky and Gates, found that the Penguin Books, London, England. p. 412. Berkefeld filters, which exclude bacteria. filtrate contained the infectious agent. 3. Olitsky, P.K., and F.L. Gates. 1921. J. Exp. Med. The infectious agent—which caused Shope’s filtrate caused a highly conta- 33:125–145. lung disease in rabbits—passed through gious, influenza-like disease in pigs— 4. Olitsky, P.K., and F.L. Gates. 1921. J. Exp. Med. 33:361–372. the filter, suggesting that it was not a albeit a more mild one than seen in 5. Lewis, P.A., and R.E. Shope. 1931. J. Exp. bacterium (3, 4). Although the duo had naturally-infected pigs. Mixing the Med. 54:361–371. perhaps isolated the influenza virus filtrate with the bacterium reproduced 6. Shope, R.E. 1931. J. Exp. Med. 54:373–385. (which they nevertheless referred to as the severe disease. He concluded—cor- 7. Smith, W., C.H. Andrewes, and P.P. Laidlaw. 1933. Lancet. 222:66–68. rectly—that the filterable agent caused 8. Andrewes, C.H., P.P. Laidlaw, and W. Smith. Text by Heather L. Van Epps the infection, which then facilitated sec- 1935. Brit. J. Exp. Path. 16:291. JEM News Editor; [email protected] ondary infection with the bacterium (6). 9. Shope, R.E. 1936. J. Exp. Med. 63:669–684. JEM © The Rockefeller University Press $8.00 803 Vol. 203, No. 4, April 17, 2006 803 www.jem.org/cgi/doi/10.1084/jem.2034fta.
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