The Spanish Flu, Epidemics, and the Turn to Biomedical Responses

Abstract

A century ago, nonpharmaceutical interventions such as school closings, restrictions on large gatherings, and isolation and quarantine were the centerpiece of the response to the Spanish Flu. Yet, even though its cause was unknown and the science of vaccine development was in its infancy, considerable enthusiasm also existed for using vaccines to prevent its spread. This desire far exceeded the scientific knowledge and technological capabilities of the time.

Beginning in the early 1930s, however, advances in virology and influenza vaccine development reshaped the relative priority given to biomedical approaches in epidemic response over traditional public health activities. Today, the large-scale implementation of nonpharmaceutical interventions akin to the response to the Spanish Flu would face enormous legal, ethical, and political challenges, but the enthusiasm for vaccines and other biomedical interventions that was emerging in 1918 has flourished.

The Spanish Flu functioned as an inflection point in the history of epidemic responses, a critical moment in the long transition from approaches dominated by traditional public health activities to those in which biomedical interventions are viewed as the most potent and promising tools in the epidemic response arsenal.

Contemporary discussions of pandemic influenza and other epidemics routinely highlight the central role biomedical interventions such as vaccines and pharmaceuticals are likely to play in preparedness and response. Yet, in recent years, severe seasonal influenza seasons, the 2009–2010 novel H1N1 influenza pandemic, and planning for a potential avian influenza pandemic have revealed the significant limitations in influenza vaccine production methods, manufacturing speed and capacity, and effectiveness. The therapeutic benefits of antiviral medications are limited, at best. For epidemics caused by pathogens other than influenza, the availability and potential value of vaccines and pharmaceuticals vary widely and are often uncertain, despite considerable enthusiasm and investment for ongoing efforts to produce new preventive and therapeutic tools for a range of potential threats.

To be sure, nonpharmaceutical interventions, such as closing schools and public gathering places or separating those infected or exposed from their communities, remain prominent features of epidemic response strategies—as seen during the 2014 Ebola outbreak in West Africa and in successive iterations of pandemic planning documents. However, their principal role and greatest value are often framed as short-term measures, minimizing the effects of an epidemic until effective vaccines or therapies can be developed, produced, and distributed.¹

A century ago, nonpharmaceutical interventions were the centerpiece of the response to the Spanish Flu, especially in US cities. Yet, even though the cause of the Spanish Flu was unknown and the science of vaccine development was still in its infancy, tremendous enthusiasm existed for using vaccines to prevent its spread. This desire far exceeded the scientific knowledge and technological capabilities of the time.

Today, the large-scale implementation of nonpharmaceutical interventions akin to the response to the Spanish Flu would face enormous legal, ethical, and political challenges. But the enthusiasm for vaccines and other biomedical interventions that was emerging in 1918 has flourished in the intervening decades, accelerated by generations of scientific advances yet tempered by the persistent challenges—particularly for influenza—that have hindered the development of broadly effective vaccines or therapeutics. The Spanish Flu functioned as an inflection point in the history of epidemic responses, a critical moment in the long transition from approaches dominated by traditional public health activities to those in which biomedical interventions are viewed as the most potent and promising tools in the epidemic response arsenal.

PUBLIC HEALTH RESPONSES TO THE SPANISH FLU

Spanish Flu arrived in the United States in spring 1918, a relatively mild first wave that largely escaped public notice at a time when American attention was increasingly directed toward the First World War.² When it returned that fall with far greater virulence, responses relied heavily on practices that had long been central to outbreak response, even before the germ theory of disease had become well established around the turn of the 20th century. As historians such as Alfred Crosby, John Barry, and Nancy Bristow have documented, health officials sought to limit the spread of the Spanish Flu through educational campaigns regarding hygiene—such as the perils of spitting and the importance of coughing into a handkerchief—as well as a spectrum of more aggressive interventions including school closings, restrictions on large gatherings, and, in some cases, isolation and quarantine.^2–5 The authority of public health departments was approaching its zenith during this period, buoyed by many successes against infectious diseases and an emerging scientific justification for their approaches to disease control that aligned comfortably with the values and sensibilities of the Progressive Era.

The degree to which nonpharmaceutical interventions—a term that would not enter into frequent use until the 1980s—were successful in limiting the effects of the Spanish Flu is a source of significant debate, particularly with respect to isolation and quarantine policies. For decades, the prevailing view was that cities that rigorously implemented closing orders for schools or public gathering places fared no better—and, in some cases, worse—than those that did not.^2,6 More recent research, supported by the US National Institutes of Health (NIH) and Centers for Disease Control and Prevention, reached different conclusions. This work, conducted as part of contemporary pandemic preparedness efforts, found that cities that implemented nonpharmaceutical interventions early and aggressively in response to Spanish Flu generally fared better than those that did not.^7,8

SPANISH FLU VACCINES, 1918–1919

There is essentially no analogous debate over the value—or more accurately, the lack thereof—of the so-called Spanish Flu vaccines that were developed and widely distributed throughout the United States during the peak of the epidemic. Within a few weeks of the onset of the second wave, physicians and other health officials, particularly at the local level, touted the availability of “revolutionary” vaccines that would in short order provide protection.⁹ For champions of Spanish Flu vaccines, a group that included health officials in cities such as New York, New York; Chicago, Illinois; and Philadelphia, Pennsylvania, the fact that the specific cause of influenza had yet to be identified did little to dampen their public enthusiasm for these interventions.^10,11

The composition of Spanish Flu vaccines varied from city to city, but all targeted one or more types of bacteria isolated from victims of influenza epidemics. Such an approach reflected the longstanding view that influenza was a bacterial disease, specifically Bacillus influenzae (now Haemophilus infuenzae), initially described in the 1890s by German bacteriologist Richard Pfeiffer.^2,3,10 Spanish Flu vaccines entered into wide use with little supporting evidence for their potential benefits, despite proclamations to the contrary from health officials such as New York City Health Commissioner Royal Copeland, and only modest attempts were made to systematically assess their effectiveness once deployed.⁴

At the national level, the Surgeon General, the American Public Health Association, and the editors of the Journal of the American Medical Association (JAMA), among others, objected to the unbridled belief among some for the value of vaccination.³ An October 1918 editorial in JAMA stated the following:

Unfortunately we as yet have no specific serum or other specific means for the cure of influenza, and no specific vaccine or vaccines for its prevention. Such is the fact, all claims and propagandist statements in the newspapers or elsewhere to the contrary notwithstanding. This being the case, efforts at treatment and prevention by serums and vaccines, now hurriedly undertaken, are simply experiments in a new field. . . . There is, therefore, no basis on which promise of protection may be made.^12(p1408)

The editorial warned physicians and, most pointedly, health officials, to keep their “head[s] level” and not “to be led into making more promises than the facts warrant.”^12(p1408)

Retrospective analyses confirmed that such warnings were justified. Reports of vaccines delivered in uncontrolled settings at times appeared to show some potential benefit, likely because they were administered when the peak of an outbreak in a community had already passed.^2,13,14 But no effect on morbidity or mortality was observed in every case in which vaccines were administered in controlled contexts, reported George W. McCoy, director of the Hygienic Laboratory, the predecessor to the NIH.¹⁴ The failure of Spanish Flu vaccines accelerated the turn away from Pfeiffer’s bacillus, as B influenzae was widely known at the time, as the presumed cause of influenza, and it promoted the development of early standards for vaccine trial design capable of providing valid assessments of effectiveness.¹⁰

With so little known in 1918 about the causative agent of Spanish Flu and essentially no evidence to suggest that any of the vaccines produced would be effective, why, then, was vaccination embraced not by hucksters or charlatans but by the leaders of some of the nation’s largest health departments? Crosby has argued persuasively that Spanish Flu vaccines had a performative function independent of their actual effectiveness.² Vaccination served as an attempt to calm nerves, a signal from health officials that the situation was under control or would be soon. Much like the earlier view regarding some nonpharmaceutical interventions used during the epidemic, Spanish Flu vaccines may thus have been principally an example of “public health theater.”

Within the scientific community, the failure to identify the cause of Spanish Flu, let alone to develop effective vaccines or other biomedical interventions against it, revealed the limits of bacteriology after a period of substantial growth and advances.¹¹ Despite the bacterial composition of each of the ineffective Spanish Flu vaccines hurried into use during the epidemic, an increasingly common view within the scientific community was that influenza was a viral disease. But, as a discipline, virology in 1918 was still “taking its first steps,” in the words of Eugenia Tognotti, lacking the tools to translate that assessment into a definitive identification, let alone into effective vaccines.^11(p107) By the early 1930s, however, virology was ascendant, as major improvements in isolating and identifying pathogens transformed the field of bacteriology into the more expansive “medical microbiology.”¹⁵ These scientific and technologic advances helped to realize the enthusiasm for vaccine-based approaches to influenza apparent during the Spanish Flu, and, in short order, to reshape the relative priority given to biomedical approaches in epidemic planning and response over traditional public health activities.

INFLUENZA VIRUS AND INFLUENZA VACCINES, 1931–2018

The principal scientific advances regarding the cause of influenza and the initial development of influenza vaccines began a little more than a decade after the end of the Spanish Flu epidemic in the United States.¹⁶ The swine influenza virus—a close relative of human influenza—was isolated and identified in 1931; 5 years later, that virus was shown to be a surviving version of the 1918 Spanish Flu itself.¹⁷ In the meantime, the first human influenza virus—subsequently referred to as influenza A virus—had been identified by Smith et al. in 1933.¹⁸ Identification of the influenza B virus, described at the time as “a new type of virus from epidemic influenza,” followed in 1940 by a group led by Thomas Francis.^19(p405)

With the causative agents of influenza conclusively identified, both research groups moved quickly to developing vaccines. By 1936, two influenza A vaccines had been produced.¹⁶ Both were grown in embryonated eggs, the approach that remains dominant in influenza vaccine production more than 80 years later. Influenza vaccines were used sparingly until the large-scale testing and introduction of a trivalent influenza vaccine for the US armed forces in the late stages of World War II.^16,20 Broader annual vaccination campaigns began after World War II, with the varying year-to-year effectiveness of the vaccine providing evidence of the annual variation of dominant strains that continues to complicate influenza vaccination efforts today.

As annual influenza vaccination steadily increased in prominence throughout the second half of the 20th century, vaccines also became central to response strategies for novel influenza strains, the kind capable, some feared, of causing epidemics on the scale of the Spanish Flu. During the 1957 “Asian Flu,” signs displayed in US pharmacies noted the speed at which scientists could collect viral strains, ship them to the NIH, manufacture vaccines, and distribute them to the public. In response to the swine influenza scare of 1976, a nationwide mass vaccination campaign was hastily planned and launched, only to be halted after a reassessment of the disease threat and concerns over vaccine safety.²¹ Issues related to vaccine development, production, and distribution were focal points of planning for a potential avian influenza pandemic in the early 2000s, and another mass vaccination program followed the emergence of a global outbreak of novel H1N1 influenza in 2009. With respect to therapeutics, the discovery of antiviral compounds beginning in the 1950s launched multiple waves of interest in their potential value in responding to influenza outbreaks and epidemics, from amantadine in the 1960s to rimantadine and oseltamivir in the 1990s and 2000s.²²

Currently, substantial resources continue to be directed at improving influenza vaccine production technologies, increasing the speed at which a vaccine is available following identification of a novel strain, and working toward a “universal” vaccine that would provide protection against most—perhaps even all—influenza strains. Progress on a universal vaccine has been hindered by the inherent difficulty of identifying a single strategy that effectively targets the highly variable and rapidly changing virus, gaps in knowledge about influenza and its transmission, the need for increased coordination among researchers, and the complex economics of vaccine markets.²³ Beyond influenza, vaccines are central to research, planning, and response efforts for a growing list of disease threats, from emerging or reemerging diseases such as Ebola and Zika to potential agents of bioterrorism such as smallpox or anthrax.

THE FUTURE OF EPIDEMIC RESPONSES

Today, biomedical responses and nonpharmaceutical interventions coexist in epidemic response plans, as they have for decades. But where discussion of novel vaccine development highlights the frontiers of scientific innovation and the prospect of powerful tools against epidemic disease, nonpharmaceutical approaches—central to public health activities for centuries—raise highly contentious legal and ethical issues regarding civil liberties, privacy, and the appropriate scope of government efforts to protect public health.²⁴ It is not surprising, therefore, that government pandemic plans commonly feature biomedical responses far more prominently than nonpharmaceutical interventions.

In the 2017 update to the US government’s Pandemic Influenza Plan, biomedical and technological approaches dominate the discussion of future priority areas, from accelerating vaccine and antiviral development to developing innovative diagnostic technologies to redesigning respiratory protective devices.¹ When “community mitigation measures” (a synonym for nonpharmaceutical interventions) are discussed, the plan explicitly notes the presumed value of those approaches before the arrival of a vaccine. Even the relatively new term “nonpharmaceutical interventions” reflects how pharmaceutical interventions (including vaccines) have become the de facto reference point for classifying epidemic responses.

School closings, masking regulations, and other traditional responses were by no means universally embraced by the public during the Spanish Flu.³ But debates over the use of aggressive public health measures that restrict individual liberty would almost certainly be far more prevalent today, fueled by growing distrust in government and experts, the decreased authority and visibility of public health compared with a century ago,²⁵ and questionable recent examples of quarantine orders by US government officials, such as those seen during the response to the 2014 Ebola outbreak.

Despite persistent concerns about vaccines—particularly routine childhood vaccination—among a small but vocal minority of parents, the public health and medical communities have long embraced vaccination as one of its most potent weapons, particularly in the context of outbreaks and epidemics. Some of the earliest signs of this enduring enthusiasm—largely shared by citizens and political leaders alike—can be seen in the response to the Spanish Flu and the specific belief in vaccines held by many health officials at the time.

That excitement surrounding vaccines served as an early signal for the increasingly privileged place that biomedical—and specifically technological—innovations would play not only in epidemic response but also in approaches to preventing and treating disease more generally. Today, those responsible for preparing for future epidemics are correct in continuing to recognize the full spectrum of tools that may contribute to responses to future threats. But the priority that biomedical responses receive in contemporary discussions of epidemic response reflects a long-term trend in 20th- and 21st-century medicine and public health that was previewed and, in part, accelerated by the response to the Spanish Flu a century ago.