The 1918-19 Spanish Influenza Pandemic and Vaccine Development
When people write about the Spanish Influenza pandemic of 1918-19, they usually start with the staggering global death toll, the huge number of people who were infected with the pandemic virus, and the inability of the medical field to do anything to help the infected. And while those factors were hallmarks of the devastating episode, researchers and health workers in the United States and Europe were confidently devising vaccines and immunizing hundreds of thousands of people in what amounted to a medical experiment on the grandest scale. What were the vaccines they came up with? Did they do anything to protect the immunized and halt the spread of the disease?
First, the numbers. In 1918 the US population was 103.2 million. During the three waves of the Spanish Influenza pandemic between spring 1918 and spring 1919, about 200 of every 1000 people contracted influenza (about 20.6 million). Between 0.8% (164,800) and 3.1% (638,000) of those infected died from influenza or pneumonia secondary to it.
A few vaccines to prevent other diseases were available at the time -- smallpox vaccine had, of course, been used for more than 100 years; Louis Pasteur had developed rabies vaccine for post-exposure prophylaxis after an encounter with a rabid animal; typhoid fever vaccines had been developed. Diphtheria antitoxin -- a medication made from the blood of previously infected animals -- had been used for treatment since the late 1800s; an early form of a diphtheria vaccine had been used; and experimental cholera vaccines had been developed. Almroth Wright had tested a whole-cell pneumococcal vaccine in South African gold miners in 1911. Manufacturers had developed and sold various mixed heat-killed bacterial stock vaccines of dubious usefulness.
In terms of knowledge of influenza as an infectious diseases, not a great deal was understood at the time. Many medical professionals thought that influenza was a specific communicable disease that presented seasonally, usually in the winter. Even so, without specific diagnostic tools, mild cases of influenza were difficult to distinguish from other acute respiratory illnesses. The tools of the time were only able to detect bacteria, not smaller pathogens.
And physicians and scientists struggled to understand whether the yearly influenza to which they were accustomed was related to the occasional widespread and highly epidemic illness of years we now know were pandemic influenza (1848-49 and 1889-90).
German scientist Richard Pfeiffer (1858-1945) claimed to have identified the causative agent of influenza in a publication in 1892 -- he described rod-shaped bacilli present in every case of influenza he examined. He was not, however, able to demonstrate Koch's postulates by causing the illness in experimental animals. Many professionals accepted his findings, though, and thought Pfeiffer's influenza bacillus, as it was called, was responsible for seasonal influenza.
But as the 1910s progressed and bacteriological methods matured, other researchers presented results that conflicted with Pfeiffer's findings. They found his organism in healthy individuals and in those suffering from illnesses that clearly were not influenza. Additionally, they looked for Pfeiffer's bacillus in influenza cases and in many instances did not find it at all. Though many physicians still believed that Pfeiffer had correctly identified the culprit, a growing number of others had begun to doubt his findings.
Those true believers had some reason to be hopeful that a vaccine could prevent influenza as the disease began its second appearance in the United States in early fall 1918. By October 2, 1918, William H. Park, MD, head bacteriologist of the New York City Health Department, was working on a Pfeiffer's bacteria influenza vaccine. The New York Times reported that Royal S. Copeland, Health Commissioner of New York City, described the vaccine as an influenza preventive and an "application of an old idea to a new disease." Park was making his vaccine from heat-killed Pfeiffer's bacilli isolated from ill individuals and testing it on volunteers from Health Department staff (New York Times, October 2, 1918). Three doses were given 48 hours apart. By October 12, he wrote in the New York Medical Journal that he was vaccinating employees from large companies and soldiers in army camps. He hoped to have evidence to demonstrate the effectiveness of the vaccine in a few weeks (Park WH, 1918).
In November, the Newark Evening News reported that 39,000 doses of Leary-Park influenza vaccine had been prepared and that most doses were used. (Timothy Leary was a professor at Tufts University School of Medicine.) Though it was too soon to tell if the vaccine was effective, "...the average person need have no fear of the results of the vaccine. Neurotic and rheumatic individuals, however, appear to be sensitive to the vaccine, while children take it with less disturbance than adults" (Newark Evening News, 1918).
By December 13, 1918, Copeland was not so confident about his department's vaccine. He told the Times that vaccines made from Pfeiffer's bacilli appeared to have no effect on influenza prevention. Rather, he was confident that a mixed bacterial vaccine (streptococcal, pneumococcal, staphylococcal, and Pfeiffer's bacilli) developed by E.C. Rosenow at the Mayo Foundation was an effective preventive. And while he thought that most people in New York had already been exposed to Spanish influenza, he mentioned that he would have Park prepare some of the Rosenow vaccine to immunize people in New York throughout the winter (New York Times, December 13, 1918). Well more than 500,000 doses of Rosenow vaccine were produced (Eyler, 2009).
University of Pittsburgh, Tulane University, and even private physicians were making their own vaccines. Convalescent serum was also used (Boston Post, January 6, 1919; Robertson & Koehler, 1918). The Deseret (UT) Evening News noted on December 14, 1918, that free vaccine was available in communities around the state.
Based on my survey of newspaper and medical journal articles from the time, it is clear that many hundreds of thousands, if not a million or more, doses of vaccines were produced during the pandemic years. (A few years ago I wrote another blog post about Rosenow's vaccine and other vaccines.)
The Editorial Committee of the American Journal of Public Health tried to put a damper on people's expectations about the vaccines. They wrote in January 1919 that the causative organism of the current influenza was still unknown, and therefore the vaccines being produced had only a chance at being directed at the right target. They noted that vaccines for secondary infections made some sense, but that all the vaccine being produced must be viewed as experimental. Acknowledging the somewhat ad hoc nature vaccine development in the current crisis, they urged that control groups be used with all the vaccines, and that the differences between control and experimental group be minimized, as to risk of exposure, time of exposure during epidemic, and so on (Editorial Committee of the American Journal of Public Health, 1919).
Certainly none of the vaccines described above prevented viral influenza infection – we know now that influenza is caused by a virus, and none of the vaccines protected against it. But were any of them protective against the bacterial infections that developed secondary to influenza? Vaccinologist Stanley A. Plotkin, MD, thinks they were not. He told us, “The bacterial vaccines developed for Spanish influenza were probably ineffective because at the time it was not known that pneumococcal bacteria come in many, many serotypes and that of the bacterial group they called B. influenzae, only one type is a major pathogen.” In other words, the vaccine developers had little ability to identify, isolate, and produce all the potential disease-causing strains of bacteria circulating at the time. Indeed, today’s pneumococcal vaccine for children protects against 13 serotypes of that bacteria, and the vaccine for adults protects against 23 serotypes.
A 2010 article, however, describes a meta-analysis of bacterial vaccine studies from 1918-19 and suggests a more favorable interpretation. Based on the 13 studies that met inclusion criteria, the authors conclude that some of the vaccines could have reduced the attack rate of pneumonia after viral influenza infection. They suggest that, despite the limited numbers of bacteria strains in the vaccines, vaccination could have led to cross-protection from multiple related strains (Chien, 2010).
It was not until the 1930s that researchers established that influenza was in fact caused by a virus, not a bacterium. Pfeiffer's influenza bacillus would eventually be named Haemophilus influenzae, the name retaining the legacy of its long-standing, though inaccurate, association with influenza. And today, influenza vaccines – as well as H. influenzae type b vaccines—are widely available to prevent illness.
Parts of this post were adapted from an earlier blog post of mine.
Cecil RL. Present status of pneumococcus vaccine. AJPH. 1919;9(8):593-594.
Chien Y, Klugman KP, Morens DM. Efficacy of whole-cell killed bacterial vaccines in preventing pneumonia and death during the 1918 influenza pandemic. JID. 2010;202(11):1639-1648.
Convalescent sera used. Boston Post. January 6, 1919.
Editorial committee of the American Public Health Association. A working program against influenza. AJPH. 1919;9(1)1-12.
Eyler JM. The state of science, microbiology, and vaccines circa 1918. Public Health Reports. 2010;125(3_suppl):27-36.
Eyler JM. The fog of research: influenza vaccine trials during the 1918–19 pandemic. Journal of the History of Medicine and Allied Sciences. 2009;64(4):401-428.
Influenza epidemic not expected here. New York Times. December 13, 1918.
Park WH. Bacteriology and possibility of anti influenza vaccine as a prophylactic. New York Medical Journal. 1918;108:15:621.
Plotkin SA. Personal correspondence. November 23, 2011.
Robertson JD, Koehler G. Preliminary report on the influenza epidemic in Chicago. AJPH. 1918;8(11)849-856.
No decision yet as to anti-grip vaccine value. Newark Evening News. November 30, 1918.
Tells of vaccine to stop influenza. New York Times. October 2, 1918.
Free vaccine for communities of state. Deseret Evening News. December 14, 1918.
Find an Influenza Serum. Kansas City Star, September 29, 1918.